柴贝止痫汤影响难治性癫痫耐药蛋白表达及海马GLU、γ-GABA含量的研究
|
摘要
难治性癫痫患者的主要特征是对绝大多数抗癫痫药物(AEDs)耐药,即使这些抗癫痫药的作用途径不同。近年来许多研究认为多药耐药基因及其编码蛋白的高表达可能是耐药机制之一。P糖蛋白、乳腺癌耐药蛋白(BCRP)、主穹窿蛋白(MVP)等耐药蛋白在难治性癫痫患者及动物模型脑部的高表达限制了病灶内AEDs的浓度。因此,抑制多药耐药蛋白的高表达来提高AEDs在病变脑组织的浓度已成为IE领域研究的热点。前期临床观察发现柴贝止痫汤联合抗癫痫药物治疗难治性癫痫可以减少患者的发作次数,减轻发作程度,而且联合使用抗癫痫药物的治疗效果优于单用柴贝止痫汤,说明柴贝止痫汤可能增敏了抗癫痫药物的疗效。根据中药多靶点效应特点,柴贝止痫汤可能通过抑制脑内多种耐药蛋白的高表达来增加脑内抗癫痫药物的浓度,抑或通过调节脑内病灶部位兴奋性神经递质和抑制性神经递质的平衡来协同抗癫痫药物提高疗效。
[目的]观察柴贝止痫汤对血脑屏障耐药蛋白P-gp、BCRP、MVP表达的影响；观察柴贝止痫汤对难治性癫痫大鼠海马CA3区细胞外液GLU、γ-GABA含量的影响。
[方法]本研究离体实验采用大鼠脑微血管内皮细胞,用谷氨酸和地塞米松孵育的方法,分别引起P-gp和BCRP表达的升高,经中药柴贝止痫颗粒水溶液干预后观察细胞P-gp和BCRP表达的变化；整体实验采用侧脑室注射海人酸的方法建立癫痫持续状态后慢性难治性癫痫大鼠模型,分设模型组、西药组、中药组、中西药组、正常组和假手术组,给药3月后观察各组大鼠脑内BCRP及MVP表达的情况并比较组间差异；同时采用微透析结合HPLC技术,检测干预后各组大鼠海马CA3区细胞外液GLU、γ-GABA的水平,比较组间差异。
[结果](1)大鼠脑微血管内皮细胞经2mM的L-谷氨酸作用3h后,P-gp及MDR1mRNA的表达较正常组升高,柴贝止痫颗粒水溶液100μg/mL、500μg/mL干预细胞后P-gp的表达较模型组降低(P<0.05),MDRlamRNA的表达较模型组降低(P<0.05)：500μg/mL干预组MDRlb mRNA的表达较模型组降低(P<0.05)；(2)细胞经100nM的地塞米松作用24h后,BCRP的表达较正常组升高,经柴贝止痫颗粒水溶液10μg/ml.100μg/ml干预后BCRP蛋白及mRNA的表达较模型组降低(P<0.05)；(3)海人酸致痫大鼠脑内BCRP的表达升高,经柴贝止痫汤及卡马西平干预后,中药组及中西药组BCRP的表达较模型组降低(P<0.05)；(4)中药组、中西药组GLU/y-GABA的值较模型组降低(P<0.05)。
[结论]柴贝止痫汤通过下调海人酸致痫大鼠脑内BCRP的表达,降低海马CA3区细胞外液中GLU/y-GABA的值,增敏抗癫痫药物,提高协同治疗难治性癫痫的疗效。
The most important feature of intractable epilepsy (IE) is resistant to many kinds of antiepileptic drugs. Some studies suggested that multidrug resistance (MDR) genes and their coding proteins excessive expression should be one of the mechanisms of drug resistance. The up-regulation of P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) in IE patients and animals limit the AEDs concentration in epileptic focus. Therefore, the inhibitions of multidrug resistance proteins expression increasing the concentration of AEDs in the lesions brain tissue are becoming more and more popular in clinical domain. Chaibei Zhixian Decoction improves the efficacy of anti-epileptic drugs and the integrative treatment can reduce seizure frequencies and severity. So we conclude that Chaibei Zhixian Decoction down-regulate the levels of multidrug resistance protein at the blood-brain barrier and increase the concentration of antiepileptic drugs in intractable patients'brains. On the other hand, Chaibei Zhixian Decoction may regulate the balance between excitatory neurotransmitters and inhibitory neurotransmitters. Therefore, Chaibei Zhixian Decoction enhance the antiepileptic effects of antiepileptic drugs.
Objective:In order to observe the antiepileptic effect of Chaibei Zhixian Decoction and investigate the mechanisms, this study will detect the protein and gene levels of BCRP and MVP after administrating with Chaibei Zhixian Decoction. Then, GLU concentration, y-GABA concentration, and the GLU/y-GABA ratio at rat hippocampal CA3region are our aims.
Methods:Primary cultures of brain microvascular endothelial cells are prepared from rats, then the3rd passage cells are exposed to L-glutamate and dexamethasone to up-regulate the expression of P-gp/MDRl and BCRP respectively, which are up-regulation as multi-drug resistant epilepsy. After treatments, the solutions were replaced with a concentration (10μg/mL,100μg/mL,500μg/mL and1mg/mL) of Chaibei Zhixian Decoction for24h. Western blot is used for the measurement of P-gp and BCRP expression and real-time PCR is used for the determination of Mdrl mRNA and BCRP mRNA amplifications.
This study rebuilt chronic intractable epileptic animal models with the method of injecting kainic acid in rat intracerebroventricular. Rats are divided into6groups randomly:normal group, sham group, model group, vehicle group, Chinese medicine group and integrative group. After3months treatment, Western blot are used to assess the expression of P-gp and BCRP in brain cortex and Realtime PCR are used to detect the amplifications of MDR1mRNA and BCRP mRNA.Microdialysis and HPLC are used to measure the concentration of GLU and γ-GABA.
Results:(1) The P-gp expression of a concentration (100μg/mL、500μg/mL) of Chaibei Zhixian Decoction group is significant lower than that of model cell group(P<0.05); the Mdrla mRNA level of a concentration (100μg/mL,500μg/mL) of Chaibei Zhixian Decoction group is lower than model group(.P<0.05); the Mdrlb mRNA amplification of a concentration (500μg/mL) of Chaibei Zhixian Decoction group is lower than model group(P <0.05).(2) Exposure to Chaibei Zhixian Decoction(10μg/ml,100μg/ml)resulted in significant decrease in protein and mRNA levels of BCRP (P<0.05); While BCRP was down-regulated, NF-κBp65expression was decreased by Chaibei Zhixian Decoction(1mg/ml)(P<0.05).(3) Injecting kainic acid in rat intracerebroventricular can up-regulate the levels of BCRP and BCRP mRNA, MVP and MVP mRNA. Treatment with Chaibei Zhixian Decoction can decrease the expression of BCRP and BCRP mRNA (P<0.05). Chinese medicine group and integrative group can decrease the level of GLU/y-GABA ratio in CA3hippocampus (P <0.05).
Conclusions:Chaibei Zhixian Decoction down-regulate the expression of BCRP at the blood-brain barrier and decrease the hippocampal CA3extracellular GLU/y-GABA ratio. These are the possible mechanisms of collaborative treatment.
[目的]观察柴贝止痫汤对血脑屏障耐药蛋白P-gp、BCRP、MVP表达的影响；观察柴贝止痫汤对难治性癫痫大鼠海马CA3区细胞外液GLU、γ-GABA含量的影响。
[方法]本研究离体实验采用大鼠脑微血管内皮细胞,用谷氨酸和地塞米松孵育的方法,分别引起P-gp和BCRP表达的升高,经中药柴贝止痫颗粒水溶液干预后观察细胞P-gp和BCRP表达的变化；整体实验采用侧脑室注射海人酸的方法建立癫痫持续状态后慢性难治性癫痫大鼠模型,分设模型组、西药组、中药组、中西药组、正常组和假手术组,给药3月后观察各组大鼠脑内BCRP及MVP表达的情况并比较组间差异；同时采用微透析结合HPLC技术,检测干预后各组大鼠海马CA3区细胞外液GLU、γ-GABA的水平,比较组间差异。
[结果](1)大鼠脑微血管内皮细胞经2mM的L-谷氨酸作用3h后,P-gp及MDR1mRNA的表达较正常组升高,柴贝止痫颗粒水溶液100μg/mL、500μg/mL干预细胞后P-gp的表达较模型组降低(P<0.05),MDRlamRNA的表达较模型组降低(P<0.05)：500μg/mL干预组MDRlb mRNA的表达较模型组降低(P<0.05)；(2)细胞经100nM的地塞米松作用24h后,BCRP的表达较正常组升高,经柴贝止痫颗粒水溶液10μg/ml.100μg/ml干预后BCRP蛋白及mRNA的表达较模型组降低(P<0.05)；(3)海人酸致痫大鼠脑内BCRP的表达升高,经柴贝止痫汤及卡马西平干预后,中药组及中西药组BCRP的表达较模型组降低(P<0.05)；(4)中药组、中西药组GLU/y-GABA的值较模型组降低(P<0.05)。
[结论]柴贝止痫汤通过下调海人酸致痫大鼠脑内BCRP的表达,降低海马CA3区细胞外液中GLU/y-GABA的值,增敏抗癫痫药物,提高协同治疗难治性癫痫的疗效。
The most important feature of intractable epilepsy (IE) is resistant to many kinds of antiepileptic drugs. Some studies suggested that multidrug resistance (MDR) genes and their coding proteins excessive expression should be one of the mechanisms of drug resistance. The up-regulation of P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) in IE patients and animals limit the AEDs concentration in epileptic focus. Therefore, the inhibitions of multidrug resistance proteins expression increasing the concentration of AEDs in the lesions brain tissue are becoming more and more popular in clinical domain. Chaibei Zhixian Decoction improves the efficacy of anti-epileptic drugs and the integrative treatment can reduce seizure frequencies and severity. So we conclude that Chaibei Zhixian Decoction down-regulate the levels of multidrug resistance protein at the blood-brain barrier and increase the concentration of antiepileptic drugs in intractable patients'brains. On the other hand, Chaibei Zhixian Decoction may regulate the balance between excitatory neurotransmitters and inhibitory neurotransmitters. Therefore, Chaibei Zhixian Decoction enhance the antiepileptic effects of antiepileptic drugs.
Objective:In order to observe the antiepileptic effect of Chaibei Zhixian Decoction and investigate the mechanisms, this study will detect the protein and gene levels of BCRP and MVP after administrating with Chaibei Zhixian Decoction. Then, GLU concentration, y-GABA concentration, and the GLU/y-GABA ratio at rat hippocampal CA3region are our aims.
Methods:Primary cultures of brain microvascular endothelial cells are prepared from rats, then the3rd passage cells are exposed to L-glutamate and dexamethasone to up-regulate the expression of P-gp/MDRl and BCRP respectively, which are up-regulation as multi-drug resistant epilepsy. After treatments, the solutions were replaced with a concentration (10μg/mL,100μg/mL,500μg/mL and1mg/mL) of Chaibei Zhixian Decoction for24h. Western blot is used for the measurement of P-gp and BCRP expression and real-time PCR is used for the determination of Mdrl mRNA and BCRP mRNA amplifications.
This study rebuilt chronic intractable epileptic animal models with the method of injecting kainic acid in rat intracerebroventricular. Rats are divided into6groups randomly:normal group, sham group, model group, vehicle group, Chinese medicine group and integrative group. After3months treatment, Western blot are used to assess the expression of P-gp and BCRP in brain cortex and Realtime PCR are used to detect the amplifications of MDR1mRNA and BCRP mRNA.Microdialysis and HPLC are used to measure the concentration of GLU and γ-GABA.
Results:(1) The P-gp expression of a concentration (100μg/mL、500μg/mL) of Chaibei Zhixian Decoction group is significant lower than that of model cell group(P<0.05); the Mdrla mRNA level of a concentration (100μg/mL,500μg/mL) of Chaibei Zhixian Decoction group is lower than model group(.P<0.05); the Mdrlb mRNA amplification of a concentration (500μg/mL) of Chaibei Zhixian Decoction group is lower than model group(P <0.05).(2) Exposure to Chaibei Zhixian Decoction(10μg/ml,100μg/ml)resulted in significant decrease in protein and mRNA levels of BCRP (P<0.05); While BCRP was down-regulated, NF-κBp65expression was decreased by Chaibei Zhixian Decoction(1mg/ml)(P<0.05).(3) Injecting kainic acid in rat intracerebroventricular can up-regulate the levels of BCRP and BCRP mRNA, MVP and MVP mRNA. Treatment with Chaibei Zhixian Decoction can decrease the expression of BCRP and BCRP mRNA (P<0.05). Chinese medicine group and integrative group can decrease the level of GLU/y-GABA ratio in CA3hippocampus (P <0.05).
Conclusions:Chaibei Zhixian Decoction down-regulate the expression of BCRP at the blood-brain barrier and decrease the hippocampal CA3extracellular GLU/y-GABA ratio. These are the possible mechanisms of collaborative treatment.
引文
[1]Banerjee PN, Filippi D, Hauser WA. The descriptive epidemiology of epilepsy-a review[J]. Epilepsy Res,2009,85:31-45.
[2]李世绰主编.中国癫痫预防与控制绿皮书[M].北京：北京大学出版社,2009：2.
[3]孟红梅,李娜,崔俐,等.吉林省部分农村地区癫痫流行病学调查[J].中风与神经疾病杂志,2010,27(12)：1108.
[4]Mohanraj R, Norrie J, Stephen LJ, et al. Mortality in adults with newly diagnosed and chronic epilepsy:a retrospective comparative study[J]. Lancet Neurol,2006,5:481-7.
[5]Lawn ND, Barnlet WR, Radhakrishnan K, et al. Injuries due to seizures in persons with epilepsy:a population based study[J]. Neurology,2004,63:1565-1570.
[6]McCagh J, Fisk JE, Baker GA. Epilepsy, psychosocial and cognitive functioning [J]. Epilepsy Res,2009,86:1-14.
[7]Kwan P, Brodie MJ. Early identification of refractory epilepsy [J]. N Engl J Med,2000, 342:314-319.
[8]吴逊,沈鼎烈.难治性癫痫[J].中华神经科杂志,1998,31：4.
[9]Kwan P, Arzimanoglou A, Berg AT, et al. Definition of drug resistant epilepsy:Consensus proposal by the ad hoc Task Force of the ILAE Commission on Therapeutic Strategies [J]. Epilepsia,2010,51 (6):1069-1077.
[10]Sillanp M, Schmidt D. Early seizure frequency and aetiology predict long-term medical outcome in childhood-onset epilepsy[J].Brain,2009,132:989-998.
[11]舒凯,陈旭,雷霆,等.难治性癫痫的规范化外科治疗[J/CD].中华临床医师杂志：电子版,2012,6(9)：2237-2275.
[12]陈光福,马启玲,贾少微,等.体外反搏对难治性癫痫患儿局灶性脑血流灌注的影响[J/CD].中华临床医师杂志电子版,2009,3(1)：140-143.
[13]Kwan P, Schachter SC, Brodie MJ. Drug-resistant epilepsy[J]. N Engl J Med,2011,365: 919-926.
[14]Rodriguez-Baeza A, Torre FR, Poca A, et al. Morphological features in human cortical brain micro vessels after head injury:a three-dimensional and immunocytochemical study [J]. Anat Rec A Discov Mol Cell Evol,2003,273(1):583-593.
[15]Pardridge WM. Blood-brain barrier drug targeting:the future of brain drug development [J].Mol Interv,2003,3(2):90-105,151.
[16]Hediger M.A., Clemencon B, Burrier R, et al. The ABCs of membrane transporters in health and disease(SLC series):introduction[J]. Molecular Aspects of Medicine,2013,34: 95-107.
[17]Murugesan N, Macdonald J, Ge S, et al. Probing the CNS microvascular endothelium by immune-guided laser-capture microdissection coupled to quantitative RT-PCR[J]. Method Mol Biol,2011,755:385-394.
[18]Danbolt NC. Glutamate uptake[J]. Prog Neurobiol,2001,65(1):1-105.
[19]Grewer C, Gameiro A, Zhang Z, et al. Glutamate forward and reverse transport from molecular mechanism to transporter-mediated released after ischemia[J]. IUBMB Life, 2008,60(9):609-619.
[20]Kanai Y, Nussberger S, Romero MF, et al. Electrogenic properties of the epithelial and neuronal high affinity glutamate transporter[J]. JBiol Chem,1995,270(28):16561-16568.
[21]Zerangue N, Kavanaugh MP. Flux coupling in a neuronal glutamate transporter [J]. Nature, 1996,383(6601):634-637.
[22]Bailey CG, Ryan RM, Thoeng AD, et al. Loss-of-function mutations in the glutamate transporter SLC1A1 cause human dicarboxylic aminoaciduria[J]. J Clin Invest.,2011, 121(1):446-453.
[23]Benediktsson AM, Marrs GS, Tu JC, et al. Neuronal activity regulates glutamate transporter dynamics in developing astrocytes[J]. GLIA,2012,60:175-188.
[24]Cohen-Kashi-Malina K, Cooper I, Teichberg V. Mechanisms of glutamate efflux at the blood-brain barrier:involvement of glial cells[J]. Journal of Cerebral Blood Flow & Metabolism,2012,32:177-189.
[25]Huang YH, Bergles DE. Glutamate transporters bring competition to the synapse[J]. Curr Opin Neurobiol,2004,14:346-352.
[26]Tzingounis AV, Wadiche JI. Glutamate transporters:Confining runaway excitation by shaping synaptic transmission[J]. Nat Rev Neurosci,2007,8:935-947
[27]Magistretti PJ. Role of glutamate in neuron-glia metabolic coupling[J]. Am J Clin Nutr, 2009,90(suppl):875S-880S.
[28]Grewer C, Gameiro A, Rauen T. SLC1 glutamate transporters[J]. Eur J Physiol,2014, 466:3-24.
[29]Kanai Y, Clemencon B, Simonin A, et al. The SLC1 high-affinity glutamate and neutral amino acid transporter family[J]. Mol Aspects Med,2013,34(2-3):108-120.
[30]Liddelow S, Temple S, Mollgard K, et al. Molecular characterization of transport mechanisms at the developing mouse blood-CSF interface:a transcriptome approach [J].PLoS ONE,2012,7(3):e33554.
[31]Daneman R, Zhou L, Agalliu D, et al. The mouse blood-brain barrier transcriptome:a new resource for understanding the development and function of brain endothelial cells[J]. PLoS ONE,2010a,5(10):e13741.
[32]Holmseth S, Dehnes Y, Huang YH, et al. The density of EAAC1(EAAT3) glutamate transporters expressed by neurons in the mammalian CNS[J]. J Neurosci,2012,32:6000-6013.
[33]Aoyama K, Watabe M, Nakaki T. Modulation of neuronal glutathione synthesis by EAAC1 and its interacting protein GTRAP3-18[J]. Amino Acid,2012,42(1):163-169.
[34]Berman AE, Chan WY, Brennan AM, et al. N-acetylcysteine prevents loss of dopaminergic neurons in the EAAC1-/-mouse[J]. Ann Neurol,2011,69:509-520.
[35]Cao L, Li L, Zuo Z. N-acetylcysteine reverses existing cognitive impairment and increased oxidative stress in glutamate transporter type 3 deficient mice[J]. Neuroscience, 2012,220:85-89.
[36]Won SJ, Yoo BH, Brennan AM, et al. EAAC1 gene deletion alters zinc homeostasis and exacerbates neuronal injury after transient cerebral ischemia[J]. J Neurosci,2010,24:87-93.
[37]Bjornsen LP, Hadera MG, Zhou Y, et al. The GLT-1(EAAT2;slcla2) glutamate transporter is essential for glutamate homeostasis in the neocortex of the mouse[J]. Journal of Neurochemistry,2014,128(5):641-649.
[38]Schmitt A, Asan E, Puschel B, et al. Celluar and regional distribution of the glutamate tramsporter GLAST in the CNS of rats:nonradioactive in SituHybridization and comparative immunocytochemistry[J]. The Journal of Neuroscience,1997,17(1):1-10.
[39]Berger UV, Hediger MA. Distribution of the glutamate transporters GLT-1(SLC1 A2) and GLAST(SLC1 A3) in peripheral organs[J]. Anat Embryol,2006,211:595-606.
[40]Shin JW, Nguyen KTD, Pow D, et al. Distribution of glutamate transporter GLAST in membranes of cultured astrocytes in the presence of glutamate transport substrates and ATP[J]. Neurochem Res,2009,34:1758-1766.
[41]Martinez-Lozada Z, Guillem AM, Flores-Mendez M, et al. GLAST/EAAT1-induced Glutamine release via SNAT3 in Bergmann glial cells:evidence of a functional and physical coupling[J]. Journal of Neurochemistry,2013,125(4):545-554.
[42]Martinez-Lozada Z, Hernandez-Kelly LC, Aguilera J, et al. Signaling through EAAT-1/ GLAST in cultured Bergmann glial cells[J]. Neurochemistry International,2011,59(6): 871-879.
[43]Miyazaki T, Takasaki C, Watanabe M. Neural circuit development and plasticity shaped by glutamate transporters [J]. Molecular Imaging for Integrated Medical Therapy and Drug Development,,2010,207-221.
[44]Tsai M-G, Tanaka K, Overstreet-Wadiche L, et al. Neuronal glutamate transporters regulate glial excitatory transmission[J]. The Journal of Neuroscience,2012,32(5): 1528-1535.
[45]Schneider N, Cordeiro S, Machtens JP, et al. Functional properties of the retinal glutamate transporters GLT-1 and EAAT5[J]. The Journal of Biological Chemistry,2014, 289:1815-1824.
[46]Mueckler M, Makepeace C. Model of the exofacial sbustrate-binding site and helical folding of the human Glutl glucose transporter based on scanning mutagenesis[J]. Biochemistry,2009,48(25):5934-5942.
[47]Thorens B, Mueckler M.Glucose transporters in the 21st century[J]. Am J Physiol Endocrinol,2010,298(2):E141-145.
[48]Augustin R. The protein family of glucose transport facilitators:It's not only about glucose after all[J]. IUBMB Life,2010,62(5):315-333.
[49]Bibert S, Hess SK, Firsov D, et al. Mouse GLUT9:evidences for a urate uniporter[J].Am J Physiol Renal Physiol,2009,297(3):F612-619.
[50]Lee YC, Huang HY, Chang CJ, et al. Mitochondrial GLUT10 facilitates dehydroascorbic acid import and protects cells against oxidative stress:mechanistic insight into arterial tortuosity syndrome [J]. Hum Mol Genet,2010,19(19):3721-3733.
[51]Alexander SPH, Mathie A, Peters JA. Guide to receptors and channels(GRAC),5th edn[J]. Br J Pharmacol,2011,164(Suppl.1):S1-S324.
[52]Guo XL, Geng MY, Du GH. Glucose transporter 1, distribution in the brain and in neural disorders:its relationship with transport of neuroactive drugs through the blood-brain barrier[J]. Biochemical Genetics,2005,43(3/4):175-187.
[53]Uldry M, Ibberson M, Hosokawa M, et al.GLUT2 is a high affinity glucosamine transporter[J]. FEBS Lett,2002,524:199-203.
[54]Devraj K, Klinger ME, Myers RL, et al.GLUT-1 glucose transporters in the blood-brain barrier:differential phosphorylation[J]. J Neurosci Res,2011,89(12):1913-1925.
[55]Hayes J D, Pulford D J. The Glut athione S-Transferase Supergene Family:Regulation of GST and the Contribution of the lsoenzymes to Cancer Chemoprotection and Drug Resistance Part Ⅰ[J]. Critical reviews in biochemistry and molecular biology,1995,30(6): 445-520.
[56]Pardridge W M, Boado R J, Farrell C R. Brain-type glucose transporter (GLUT-1) is selectively localized to the blood-brain barrier. Studies with quantitative western blotting and in situ hybridization[J]. Journal of Biological Chemistry,1990,265(29):18035-18040.
[57]Russell R R, Bergeron R, Shulman G I, et al. Translocation of myocardial GLUT-4 and increased glucose uptake through activation of AMPK by AICAR[J]. American Journal of Physiology-Heart and Circulatory Physiology,1999,277(2):H643-H649.
[58]Hughes V A, Fiatarone M A, Fielding R A, et al. Exercise increases muscle GLUT-4 levels and insulin action in subjects with impaired glucose tolerance[J]. American Journal of Physiology-Endocrinology And Metabolism,1993,264(6):E855-E862.
[59]Megeney L A, Neufer P D, Dohm G L, et al. Effects of muscle activity and fiber composition on glucose transport and GLUT-4[J]. American Journal of Physiology-Endocrinology And Metabolism,1993,264(4):E583-E593.
[60]Beltran FA, Acuna AI, Miro MP, et al. Ascorbic acid-dependent GLUT3 inhibition is a critical step for switching neuronal metabolism[J]. Journal of Cellular Physiology,2011, 226(12):3286-3294.
[60]Carayannopoulos MO, Xiong FX, Jensen P, et al. GLUT3 gene expression is critical for embryonic growth, brain development and survival [J]. Molecular Genetics and Metablism,2014,online
[60]Brown K, Heller DS, Zamudio S, et al. Glucose transporter 3(GLUT3) protein expression in human placenta across gestation[J]. Placenta,2011,32(12):1041-1049.
[63]Scheffer I E. GLUT1 deficiency A glut of epilepsy phenotypes[J]. Neurology,2012,78(8): 524-525.
[64]Leary L D, Wang D, Nordli D R, et al. Seizure Characterization and Electroencepha-lographic Features in Glut-1 Deficiency Syndrome[J]. Epilepsia,2003,44(5):701-707.
[65]Hall GV, Stromstad M, Rasmussen P, et al. Blood lactate is an important energy source for the human brain[J]. Journal of Cerebral Blood Flow & Metabolism,2009.,29:1121-1129.
[66]Lutas A, Yellen G. The ketogenic diet:metabolic influences on brain excitability and epilepsy[J]. Trend in Neurosciences,2013,36(1):32-40.
[67]Simpson IA, Carruthers A, Vannucci SJ. Supply and demand in cerebral energy metabolism:the role of nutrient transporters [J]. Journal of Cerebral Blood Flow & Metabolism,2007,27:1766-1791.
[68]Dienel GA. Fueling and imaging brain activation[J].ASN Neruo,2012,4(5):e00093.
[69]Harris JJ, Jolivet R, Attwell D. Synaptic energy use and supply[J]. Neuro,2012,75(5): 762-777.
[70]Gandhi GK, Cruz NF, Ball KK, et al. Astrocytes are poised for lactate trafficking and release from activated rain and for supply of glucose to neurons[J]. Journal of Neurochemistry,2009,111:522-536.
[71]Rouach N, Koulakoff A, Abudara V, et al. Astroglial metabolic networks sustain hippocampal synaptic transmission[J]. Science,2008,332:1551-1555.
[72]Leroy C, Pierre K, Simpson I A, et al. Temporal changes in mRNA expression of the brain nutrient transporters in the lithium-pilocarpine model of epilepsy in the immature and adult rat[J]. Neurobiology of disease,2011,43(3):588-597.
[73]Hildebrand M S, Damiano J A, Mullen S A, et al. Glucose metabolism transporters and epilepsy:Only GLUT1 has an established role[J]. Epilepsia,2014.
[74]Gerhart D Z, Leino R L, Taylor W E, et al. GLUT1 and GLUT3 gene expression in gerbil brain following brief ischemia:an in situ hybridization study [J]. Molecular brain research, 1994,25(3):313-322.
[75]Simpson I A, Chundu K R, Davies-Hill T, et al. Decreased concentrations of GLUT1 and GLUT3 glucose transporters in the brains of patients with Alzheimer's disease [J]. Annals of neurology,1994,35(5):546-551.
[76]Gronlund K M, Gerhart D Z, Leino R L, et al. Chronic seizures increase glucose transporter abundance in rat brain[J]. Journal of Neuropathology & Experimental Neurology,1996,55(7):832-840.
[77]Ueno M, Nishi N, Chiba TNY, et al. Immunoreactivity of glucose transporter 5 is located in epithelial cells of the choroid plexus and ependymal cells[J]. Neuroscience,2014,260: 149-157.
[78]Page KA, Chan O, Arora J, et al. Effects of fructose vs glucose on regional cerebral blood flow in brain regions involved with appetite and reward pathways[J]. JAMA,2013,309(1): 63-70.
[79]Ibberson M, Riederer BM, Uldry M, et al. Immunolocalization of GLUTX1 in th testis and to specific brain areas and vasopressin-containing neurons[J]. Endocrinology,2002, 143(1):276-284.
[80]Gomez O, Romero A, Terrado J, et al. Differential expression of glucose transporter GLUT8 during mouse spermatogenesis[J]. Reprduction,2006,131:63-70.
[81]Gavlik V, Schmidt S, Scheepers A, et al. Targeted disruption of Slc2a8(GLUT8) reduces motility and mitochondrial potential of spermatozoa[J]. Mol.Membr.Biol,2008,25:224-235.
[82]Reagan LP, Rosell DR, Alves SE, et al. Glut8 glucose transporter is localized to excitatory and inhibitory neurons in the rat hippocampus [J]. Brain Res,2002,932:129-134.
[83]Membrez M, Hummler E, Beemann F, et al. GLUT8 is dispensable for embryonic development but influences hippocampal neurogenesis and heart function[J]. Mol Cell Biol,2006,26:4268-4276.
[84]Schmidt S, Joost HG, Schurmann A. GLUT8, the enigmatic intracellular hexose ransporter[J]. Am JPhysiol Endocrinol Metab,2009,296:E614-618.
[85]Mora F, Segovia G, Arco A, et al. Stress, neurotransmitters, corticosterone and body-brain intergration[J]. BRAIN RESEARCH,2012,1476:71-85.
[86]Jurcovicova J.Glucose transport in brain-effect of inflammation[J].Endocrine Regulations, 2014,48(1):35-48.
[87]Bourgeois F, Coady M J, Lapointe J Y. Determination of transport stoichiometry for two cation-coupled myo-inositol cotransporters:SMIT2 and HMIT[J]. The Journal of physiology,2005,563(2):333-343.
[88]Di Daniel E, Mok M H S, Mead E, et al. Evaluation of expression and function of the H+/myo-inositol transporter HMIT[J]. BMC cell biology,2009,10(1):54.
[89]Didaniel E, Kew J N, Maycox P R. Investigation of the H+-myo-inositol transporter (HMIT) as a neuronal regulator of phosphoinositide signalling[J]. Biochemical Society Transactions,2009,37(5):1139.
[90]Wood I S, Hunter L, Trayhurn P. Expression of Class III facilitative glucose transporter genes (GLUT-10 and GLUT-12) in mouse and human adipose tissues [J]. Biochemical and biophysical research communications,2003,308(1):43-49.
[91]D Serrano I, MB Ribeiro M, ARB Castanho M. A focus on glucose-mediated drug delivery to the central nervous system[J]. Mini reviews in medicinal chemistry,2012, 12(4):301-312.
[92]Broer S, Palacin M. The role of amino acid transporters in inherited and acquired diseases [J]. Biochem J,2011,436:193-211.
[93]Chen NH, Reith ME, Quick MW.Synaptic uptake and beyond:the sodium- and chloride-dependent neurotransmitter transporter family SLC6[J]. Pflugers Arch,2004, 447:519-531.
[94]Broer S. The SLC6 orphans are forming a family of amino acid transporters [J]. NeurochemInt,2006,48(6-7):559-567.
[95]Madsen KK, White HS, Schousboe A. Neuronal and non-neuronal GABA transporters as targets for antiepileptic drugs[J]. Pharmacol Ther,2010,125:394-401.
[96]Jin XT, Galvan A, Wichmann T, et al. Localization and function of GABA transporters GAT-1 and GAT-3 in the basal ganglia[J]. Fornt Syst Neurosic,2011,5:63.
[97]Kristensen AS, Andersen J, Jorgensen TN, et al. SLC6 neurotransmitter transporters: structure, function and regulation[J].Pharmacol Rev,2011,63:585-640.
[98]Schousboe A, Madsen KK, Barker-Haliski ML, et al. The GABA synapse as a target for antiepileptic drugs:a historical overview focused on GABA transporters [J]. Neurochemical Research,2014,3 doi:10.1007/sl 1064-014-1263-9.
[99]Pramod AB, Foster J, Carvelli L, et al. SLC6 transporters:structure, function, regulation, disease association and therapeutics [J]. Molecular Aspects of Medicine.,2013,34:197-219.
[100]Rudnick G, Kramer R, D.Blakely R, et al. The SLC6 transporters:perspectives on structure, functions, regulation, and models for transporter dysfunction[J]. Pflugers Arch-Eur J Physiol,2014,466:25-42.
[101]Plos TW, Noriega LG, Nomura M, et al. The bile acid membrane receptor TGR5 as an emerging target in metabolism and inflammation[J].J Hepatol,2011,54(6):1263-1272.
[102]Stieger B. The role of the sodium-taurocholate cotransporting polypeptide (NTCP) and of the bile salt export pump (BSEP) I physiology and pathophysiology of bile formation [J]. Handb.Exp.Pharmacol,2011,201:205-259.
[103]Akita H, H.Suzuki K, K.Ito S, et al. Characterization of bile acid transport mediated by multidrug resistance associated protein 2 and bile salt export pump [J]. Biochim Biophys Acta,2001,1511:7-16.
[104]D.Lee S, J.Thornton S, Sachs-Barrable K, et al. Evaluation of the contribution of the ATP binging cassette transporter, p-glycoprotein, to in vivo cholesterol homeostasis[J]. Mol. Pharmaceutics,2013,10(8):3203-3212.
[105]Telbisz A, Hegedus C, Baradi A, et al. Regulation of the function of the human ABCG2 multidrug transporter by cholesterol and bile acids:effects of mutations in potential substrate-and steroid-binging sites[J]. Drug Metab-Dispos,2014,42(4):575-585.
[106]Silva TC, E.Polli J, W.Swaan P. The solute carrier family 10 (SLC10):beyond bile acid transport [J]. Molecular Aspects of Medicine,,2013,,34:252-269.
[107]Burger S, Doring B, Hardt M, et al. Co-expression studies of the orphan carrier protein Slc10a4 and the vesicular carriers VAChT and VMAT2 in the rat central and peripheral nervous system[J].Neurosicence,2011,193:109-121.
[108]Halestrap AP, Meredith D. The SLC16 gene family-from monocardoxylate transporters (MCTs) to aromatic amino acid transporters and beyond[J]. Pflugers Arch.,2004,447: 619-628.
[109]Visser WE, Friesema EC, Visser TJ. Thyroid hormone transporters:the knowns and the unknowns[J]. Mol. Endocrinol,2011,25:1-14.
[110]Halestrap AP, C.Wilson M. The monocarboxylate transporter family-role and regulation [J]. IUBMB Life,2012,64(2):109-119.
[111]Halestrap AP. The monocardoxylate transporter family-structure and functional charac-terization[J]. IUBMU Life,2012.64(1):1-9.
[112]Cheng Z, Liu H, Yu N, et al. Hydrophilic anti-migraine triptans are substrates for OAPT1A2, a transporter expressed at human blood-brain barrier[J]. Xenobiotica,2012, 42(9):880-890.
[113]Bronger H, Konig J, Kopplow K, et al. ABCC drug efflux pumps and organic anion uptake transporters in human gliomas and the blood-tumor barrier[J]. Cancer Res,2005, 65:11419-11428.
[114]Alkemade A, Friesema EC, Kalsbeek A, et al. Expression of thyroid hormone trans-porters in the human hypothalamus[J]. JClin Endocrinol Metab,2011,96(6):E967-971.
[115]Roberts LM, Woodford K, Zhou M, et al. Expression of the thyroid hormone transporters monocarboxylate transporter-8 (SLC16A2) and organic ion transporter-14 (SLCO1C1) at the blood-brain barrier[J]. Endocrinology,2008,149(12):6251-6261.
[116]Fenner KS, Jones HM, Ullah M, et al. The evolution of the OATP hepatic uptake transport protein family in DMPK sciences:from obscure liver transporters to key determinants of hepatobiliary clearance[J]. Xenobiotica,2012,42(1):28-45.
[117]Obaidat A, Roth M, Hagenbuch B. The expression and function of organic anion transporting polypeptides in normal tissues and in cancer[J]. Annu Rev Pharmacol Toxicol,2012,52:135-151.
[118]Koepsell H. The SLC22 family with transporters of organic cations, anions and zwitterions[J] Molecular Aspects of Medicine.,2013,34:413-435.
[119]Cui M, Aras R, Christian WV, et al. The organic cation transporter-3 is a pivotal modulator of neurodegeneration in the nigrostriatal dopaminergic pathway [J]. Proc Natl Acad Sci U.S.A,2009,106:8043-8048.
[120]Gasnier B. The SLC32 transporter, a key protein for the synaptic release of inhibitory amino acids[J]. Pflugers Arch,2004,47(5):756-759.
[121]Pillai SM, Meredith D. SLC36A4 (hPAT4) is a high affinity amino acid transporter when expressed in Xenopus laevis oocytes[J]. JBiol Chem,2011,286(4):2455-2460.
[122]Sundberg BE, Waag R, Jacobsson JA, et al. The evolutionary history and tissue mapping of amino acid transporters belonging to solute carrier families SLC32, SLC36, and SLC38[J]. JMol Neruosci,2008,35(2):179-193.
[123]Schioth HB., Roshanbin S., Hagglund MG.A., et al. Evolutionary origin of amino acie transporter families SLC32, SLC36 and SLC38 and physiological, pathological and therapeutic aspects[J]. Molecular Aspects of Medicine,2013,34:571-581.
[124]Hagglund M.G., Sreedharan S., Nilsson VC.O, et al. Identification of SLC38A7 (SNAT7) protein as a glutamine transporter expressed in neurons[J]. J. Biol. Chem.,2011,286: 20500-20511.
[125]Traiffort E., O'Regan S., Ruat M., The choline transporter-like family SLC44:properties and roles in human diseases[J]. Molecular Aspects of Medicine,2013,34:646-654.
[126]Machova E., O'Regan S., Newcombe J., et al. Detection of choline transporter-like 1 protein CTL1 in neuroblastoma & glioma cells and in the CNS, and its role in choline uptake[J]. Journal of Neurochemistry,2009,110:1297-1309.
[127]Miller DS. Regulation of P-glycoprotein and other ABC drug transporters at the blood-brain barrier[J]. Trends Pharmacol Sci,2010,31(6):246-254.
[128]Mahringer A, Ott M, Reimold I, et al. The ABC of the blood-brain barrier-regulation of drug efflux pumps[J]. Current Pharmaceutical Design,2011,17(26):2762-2770(9).
[129]Luna-Tortos C, Fedrowitz M, Loscher W. Several major antiepileptic drugs are substrates for human P-glycoprotein[J]. Neuropharmacology,2008,55(8):1364-1375.
[130]Zhang C, Kwan P, Zuo Z, et al. The transporter of antiepileptic drugs by P-glycoprotein [J]. Adv Drug Deliv Rev,2012,64(10):930-942.
[131]Agarwal S, Hartz AM, Elmquist WF, et al. Breast cancer resistance and P-glycoprotein in brain cancer:two gatekeepers team up[J]. Curr Pharm Des,2011,17:2793-2802.
[132]Uchida Y, Ohtsuki S, Katsukura Y, et al. Quantitative targeted absolute proteomics of human blood-brain barrier transporters and receptors [J]. JNeurochem,2011,117:333-345.
[133]Agarwal S, Sane R, Gallardo JL, et al. Distribution of gefitinib to the brain is limited by P-glycoprotein (ABCB1) and breast cancer resistance protein (ABCG2)-mediated active efflux[J]. J Pharmacol Exp Ther,2010,334:147-155.
[134]Paspalas CD, Perley CC, Venkitaramani DV, et al. Major vault protein is expressed along the nucleus-neurite axis and associates with mRNAs in cortical neurons[J]. Cerebral Cortex,2009,19:1666-1677.
[135]Balan S, Iekshmi S, Radha K, et al. Major vault protein (MVP) gene polymorphisms and drug resistance in mesial temporal lobe epilepsy with hippocampal sclerosis[J]. Gene,2013,526(2):449-453.
[136]Liu B, Wang T, Wang L, et al. Up-regulation of major vault protein in the frontal cortex of patients with intractable frontal lobe epilepsy [J].Journal of the Neurological Science, 2011,308(1-2):88-93.
[137]Sisodiya SM, Marinian L, Scheffer GL, et al. Vascular colocalization of P-glycoprotein, multidrug-resistance associated protein1, breast cancer resistance protein and major vault protein in human epileptogenic pathologies[J]. Neuropathology and Applied Neurobi-ology,2006,32(1):51-63.
[138]Kovacs R, Raue C, Gabriel S, et al. Functional test of multidrug transporter activity in hippocampal-neocortical brain slices from epileptic patients[J]. Journal of Neuroscience Methods,2011,200(2):164-172.
[139]Wilhelm I, Fazakas C, Krizbai IA. In vitro models of the blood-brain barrier[J].Acta Neurobiol Exp(Wars),2011,71:113-128.
[140]Redzic Z. Molecular biology of the blood-brain and the blood-cerebrospinal fluid barriers:similarities and differences[J]. Fluids Barriers CNS,2011,8:3.
[141]Liddelow SA, Temple S, Mollgard K, et al. Molecular characterization of transport mechanisms at the developing mouse blood-CSF interface:a transcriptome approach[J]. PLoS One,2012,7:e33554.
[142]Cardoso FL, Brites D, Brito MA. Looking at the blood-brain barrier:molecular anatomy and possible investigation approaches[J].Brain Research Reviews,2010,64:328-363.
[143]Wolburg H, Lippoldt A. Tight junctions of the blood-brain barrier:development, composition and regulation[J]. Vascular Pharmacology,2002,323-337.
[144]Luissint AC, Artus C, Glacial F, et al. Tight junctions at the blood brain barrier: physiological architecture and disease-associated dysregulation[J]. Fluids and Barriers of the CNS,2012,9:23.
[145]Terry S, Nie M, Matter K, et al. Rho signaling and tight junction functions[J]. Physiology,2010,25:16-26.
[146]Lee HS, Namkoong K, Kim DH, et al. Hydrogen peroxide-induced alterations of tight junction proteins in bovine brain microvascular endothelial cells[J]. Microvascular Research,2004,68(3):231-238.
[147]Persidsky Y, Ramirez SH, Haorah J, et al. Blood-brain barrier:structural components and function under physiologic and pathologic conditions [J]. J Neuroimmune Pharmacol, 2006,1(3):223-236.
[148]Weiss N, Miller F, Cazaubon S, et al. The blood-brain barrier in brain homeostasis and neurological diseases[J]. Biochim Biophys Acta,2009,
[149]Engelhardt B, Ransohoff RM. Capture, crawl, cross:the T cell code to breach the blood-brain barriers[J]. Trends Immunol,2012,33:519-589.
[150]Hawkins BT, Abbruscato TJ, Egleton RD, et al. Nicotine increases in vivo blood-brain barrier permeability and alters cerebral microvascular tight junction protein distribution [J].Brain Res,2004,1027:48-58.
[151]Brown RC, Davis TP. Hypoxia/aglycemia alters expression of occludin and actin in brain endothelial cells[J]. Biochem Biophys Res Commun,2005,327:1114-1123.
[152]Dorfel MJ, Huber O. Modulation of tight junction structure and function by kinases and phosphatases targeting occludin[J] Journal of Biomedicine and Biotechnology,2012, 2012:807356.
[153]Itallie CMV, Fanning AS, Holmes J, et al. Occludin is required for cytokine-induced regulation of tight junction barriers[J]. Journal of Cell Science,2010,123(16):2844-2852.
[154]Buschmann MM, Shen L, Rajapakse H, et al. Occludin OCEL-domain interactions are required for maintenance and regulation of the tight junction barrier to macromolecular flux[J]. Mol. Biol. Cell,2013,24(19):3056-3068.
[155]Rao R. Occludin phosphorylation in regulation of epithelial tight junctions[J]. Ann of the New York Academy of Sciences,2009,1165:62-68.
[156]Itallie CMV, Anderson JM. Claudin interactions in and out of the tight junction[J]. Tissue Barrier,2013,1(3):e25247.
[157]Cording J, Berg J, Kading N, et al. In tight junctions, claudins regulate the interactions between occludin, tricellulin and marvelD3, which, inversely, modulate claudin oligomerization[J].Journal of Cell Science,2012,126:554-564.
[158]Kubota K, Furuse M, Sasaki H, et al. Ca2+-independent cell-adhesion activity of claudins, a family of integral membrane proteins localized at tight junctions[J].Curr Biol, 1999,9:1035-1038.
[159]Overgaard CE, Daugherty BL, Mitchell LA, et al. Claudins:control of barrier function and regulation in response to oxidant stress[J]. Antioxid. Redox signal,2011,15(5):1179-1193.
[160]Angelow S, Ahlstrom R, Yu ASL. Biology of Claudins[J]. Am J Physiol Renal Physiol, 2008,295:F867-F876.
[161]Gunzel D, Yu ASL. Claudins and the modulation of tight junction permeability [J].Physiol.Rev,2013,93:525-569.
[162]Nitta T, Hata M, Gotoh S, et al. Size-selective loosening of the blood-brain barrier in claudin-5-deficient mice[J]. J Cell Biol,2003,161:653-660.
[163]Jia W, Lu R, Martin TA, et al. The role of claudin-5 in blood-brain barrier (BBB) and brain metastases[J]. Mol Med Rep,2014,9(3):779-785.
[164]Fanning AS, Anderson JM. Zonula occludens-1 and -2 are cytosolic scaffolds that regulate the assembly of cellular junctions[J].Ann N YAcad Sci,2009,1165:113-120.
[165]Bauer H, Zweimueller-Mayer J, Steinbacher P, et al. The dual role of Zonula Occludens (ZO) proteins[J]. Journal of Biomedicine and Biotechnology,2010,2010:402593.
[166]Bauer B. Targeting regulation of ABC transporters at the blood-brain barrier to improve pharmacotherapy of CNS disorders[J]. International Drug Discovery,2010:76-79.
[167]Ghost C, Vikram P, Jorge GM, et al. Blood-brain barrier P450 enzymes and multidrug transporters in drug resistance:a synergistic role in neurological diseases[J]. Current Drug Metabolism,2011,12(8):742-749.
[168]Marchi N, Angelov L, Masaryk T, et al. Seizure-promoting effect of blood-brain barrier disruption[J].Epilepsia,2007,48(4):732-742.
[169]Pizzini FB, Farace P, Manganotti P, et al. Cerebral perfusion alterations in epileptic patients during peri-ictal and post-ictal phase:PASL vs DSC-MRI [J]. Magn Reson Imaging,2013,31(6):1001-1005.
[170]Bek S, Kasikci T, Koc G, et al. Cerebral vasomotor reactivity in epilepsy patients[J]. J Neurol,2010,257(5):833-838.
[171]Choy M, Wells JA, Thomas DL, et al. Cerebral blood flow changes during pilocarpine-induced status epilepticus activity in the rat hippocampus[J].Exp.Neurol,2010,225(1): 196-201.
[172]Badawy RA, Wogrin SL, Lai A, et al. Cortical excitability changes correlate with fluctuations in glucose levels in patients with epilepsy [J]. Epilepsy Behav,2013,27(3): 455-460.
[173]Akman CI, Ichise M, Olsavsky A, et al..Epilepsy duration impacts on brain glucose metabolism in temporal lobe epilepsy:results of voxel-based mapping[J].Epilepsy Behav,2010,17(3):373-380.
[174]Lutas A, Yellen G. The ketogenic diet:metabolic influences on brain excitability and epilepsy [J].Trends Neurosic,2013,36(1):32-40.
[175]Lee EM, Park GY, Im KC, et al. Changes in glucose metabolism and metabolites during the epileptogenic process in the lithium-pilocarpine model of epilepsy [J]. Epilepsia,2012, 53(5):860-869.
[176]Hildebrand MS, Damiano JA, Mullen SA, et al. Glucose metabolism transporters and epilepsy:only GLUT1 has an established role[J].Epilepsia,2014,55(2):e18-e21.
[177]Marin-Valencia I, Good LB, Ma Q, et al. Glutl deficiency (G1D):epilepsy and metabolic dysfunction in a mouse model of the most common human phenotype[J]. Neurobiology of Disease,2012,48(1):92-101.
[178]Vieker S, Schmitt J, Langler A, et al. Unusual sensitivity to steroid treatment in intractable childhood epilepsy suggests GLUT1 deficiency syndrome[J]. Neuropediatrics, 2012,43(5):275-278.
[179]Crino PB, Jin H, Shumate MD, et al. Increased expression of the neuronal glutamate transporter (EAAT3/EAAC1) in hippocampal and neocortical epilepsy [J]. Epilepsia, 2002,43(3):211-218.
[180]van der Hel WS, Verlinde SA, Meijer DH, et al. Hippocampal distribution of vesicular glutamate transporter 1 in patients with temporal lobe epilepsy[J]. Epilepsia,2009,50(7): 1717-1728.
[181]Liu B, Niu L, Shen MZ, et al. Decreased astroglial monocarboxylate transporter 4 expression in temporal lobe epilepsy[J]. Mol Neurobiol,2014,online.doi:10.1007/ sl2035-013-8619-z.
[182]Kong Q, Takahashi K, Schulte D, et al. Increased glutamate transporter EAAT2 expression reduces epileptogenic processes following pilocarpine-induced status epilepticus[J]. Neurobiol Dis.,2012,47(2):145-154.
[183]Lane MC,Jackson JG, Krizman EN, et al. Genetic deletion of the neuronal glutamate transporter, EAAC1, results in decreased neuronal death after pilocarpine-induced status epilepticus[J]. Neurochem Int,2013,online, doi:dx.doi.org/10.1016/j.neuint.2013.11.013
[184]Smeland OB, Hadera MG, McDonald TS, et al. Brain mitochondrial metabolic dysfunction and glutamate level reduction in the pilocarpine model of temporal lobe epilepsy in mice[J]. Journal of Cerebral Blood Flow & Metabolism,2013,33:1090-1097.
[185]Sepkuty JP, Cohen AS, Eccles C, et al. A neuronal glutamate transporter contributes to neurotransmitter GABA synthesis and epilepsy[J]. J Neurosci,2002,22(15):6372-6379.
[186]Kwan P, Schachter SC, Brodie MJ. Drug-resistant epilepsy[J]. N Engl J Med,2011,365: 919-926.
[187]Postschka H. Role of CNS efflux drug transporters in antiepileptic drug delivery: overcoming CNS efflux drug transport[J]. Adv Drug Deliv Rev,2012,64(10):943-952.
[188]Marchi N, Gonzalez-Martinez J, Nguyen MT, et al. Transporters in drug-refractory epilepsy:clinical significance [J]. Clinical Pharmacology & Therapeutics,2010,87 (1): 13-15.
[189]Lazarowski A, Czornyj L, Lubienieki F, et al. ABC transporters during epilepsy and mechanisms underlying multidrug resistance in refractory epilepsy [J]. Epilepsia,2007, 48(s5):140-149.
[190]Balan S, Iekshmi S, Radha K, et al. Major vault protein (MVP) gene polymorphisms and drug resistance in mesial temporal lobe epilepsy with hippocampal sclerosis [J]. Gene, 2013,526(2):449-453.
[191]Sillanpaa M, Schmidt D. Natural history of treated childhood-onset epilepsy: prospective, long-term population-based study[J].Brain,2006,129(3):617-624.
[192]Jackson GD. Epilepsy:hippocampal sclerosis-are we speaking the same language?[J]. Nature Review Neurology,2013,9:548-549.
[193]van Breemen MS, Wilms EB, Vecht CJ. Epilepsy in patients with brain tumours: epidemiology, mechanisms, and management[J]. Lancet Neurol,2007,6:421-430.
[194]Picot MC, Baldy-Moulinier M, Daures JP, et al. The prevalence of epilepsy and pharmacoresistant epilepsy in adults:a population-based study in a Western European country[J].Epilepsia,2008,49:1230-1238.
[195]Marchi N, Betto G, Fazio Q, et al. Blood-brain barrier damage and ain penetration of antiepileptic drugs:role of serum proteins and brain edema[J]. Epilepsia,2009,50:664-677.
[196]Chen YH, Wang CC, Xiao X, et al. Multidrug resistance-associated protein 1 decreases the concentrations of antiepileptic drugs in cortical extracellular fluid in amygdale kindling rats[J]. Acta Pharmacol Sin,2013,34(4)-473-479.
[197]Arican N, Kaya M, Kalayci R, et al. Effects of lipopolysaccharide on blood-brain barrier permeability during pentylenetetrazol-induced epileptic seizures in rats[J]. Life Sci,2006, 79:1-7.
[198]Marchi N, Angelov L, Masaryk T, et al. Seizure-promoting effect of blood-brain barrier disruption[J].Epilepsia,2007,48:732-742.
[199]Kaya M, Gurses C, Kalayci R, et al. Morphological and functional changes of blood-brain barrier in kindled rats with cortical dysplasia[J].Brain Res,2008,1208:181-191.
[200]Ahishali B, Kaya M, Orhan N, et al. Effects of levetiracetam on blood-brain barrier disturbances following hyperthermia-induced seizures in rats with cortical dysplasia[J]. Life Sci,2010,87:609-619.
[201]Rigau V, Morin M, Rousset MC, et al. Angiogenesis is associated with blood-brain barrier permeability in temporal lobe epilepsy[J].Brain,2007,130:1942-1956.
[202]Morin-Brureau M, Lebrun A, Rousset MC, et al. Epileptiform activity induces vascular remodeling and Zonula occludens 1 down-regulation in organotypic hippocampal cultures:role of VEGF signaling pathways[J]. J Neurosci,2011,31:10677-10688.
[203]Lamas M, Gonzalez-Mariscal L, Gutierrez R. Presence of claudins mRNA in the brain: selective modulation of expression by kindling epilepsy[J]. Brain Res Mol Brain Res, 2002,104:250-254.
[1]Schayer RW, Reilly MA. In vivo formation and catabolism of 14C-histamine in mouse brain[J]. Journal of Neurochemistry,1970,17(12):1649-1655.
[2]Pardridge WM. Brain drug targeting:the future of brain drug development[J]. Cambridge, UK:Cambridge University Press,2001.
[3]Pardridge WM. The blood-brain barrier:bottleneck in brain drug developmen[J]. NeuroRx,2005,2:3-14.
[4]Chen Y, Liu LH. Modern methods for delivery of drugs across the blood-brain barrier[J]. Adv Drug Deliv Rev,2012,64:640-665.
[5]Banks WA. Drug transport into the central nervous system:using newer findings about the blood-brain barriers[J]. Drug Deliv and Transl Res,2012,2:152-159.
[6]Alyautdin R, Khalin I, Nafeeza MI, et al. Nanoscale drug delivery systems and the blood-brain barrier[J]. International Journal of Nanomedicine,2014,9:795-811.
[7]Pardridge WM. Drug transport across the blood-brain barrier[J]. Journal of Cerebral Blood Flow & Metabolism,2012,32:1959-1972.
[8]Baum L, Kwan P. Antiepileptic drug delivery[J]. Adv Drug Deliv Rev,2012,64:885-886.
[9]Matsson P, Pedersen JM, Norinder U, et al. Identification of novel specific and general inhibitors of the three major human ATP-binding cassette transporters P-gp, BCRP, and MRP2 among registered drugs[J]. Pharmaceutical Research,2009,26(8):1816-1831.
[10]Ben-Menachem E. Medical management of refractory epilepsy-Practical treatment with novel antiepileptic drugs[J]. Epilepsia,2014,55(sl):3-8.
[11]Perucca P, Gilliam FG. Adverse effects of antiepileptic drugs[J]. The Lancet Neurology, 2012,11(9):792-802.
[12]Kinderen RJA, Evers SMAA, Rinkens R, et al. Side-effects of antiepileptic drugs:the economic burden[J]. Seizure:European Journal of Epilepsy,2014,23(3):184-190.
[13]Kr PS, Jangra MK, Yadav AK. Herbal and synthetic approaches for the treatment of epilepsy[J]. Int J Nutr Pharmacol Neurol Dis,2014,4:43-52.
[14]Pearl PL, Drillings IM, Conry JA. Herbs in epilepsy:evidence for efficacy, toxicity, and interactions [J]. Seminars in Pediatric Neurology,2011,18(3):203-208.
[15]Yu CP, Tsai SY, Kao LJ, et al. A Chinese herb formula decreases the monocarboxylate transporter-mediated absorption of valproic acid rats[J]. Phytomedicine,2013,20(7):648-653.
[16]Fong SYK, Gao Q, Zuo Z. Interaction of carbamazepine with herbs, dietary supplements, and foods:a systematic review[J]. Evidence-Based Complementary and Alternative Medicine,2013,2013:898261.
[17]Samuels N, Finkelstein Y, Singer SR, et al. Herbal medicine and epilepsy:proconvulsive effects and interactions with antiepileptic drugs[J]. Epilepsia,2008,49(3):373-380.
[18]逄冰,刘文科,周强,等.芳香药物效用探析[J].中医杂志,2013,54(18)：1616-1618.
[19]何俊余.引经药为何能引经报使[J].世界中医药,2011,6(6)：521.
[20]吴雪,欧阳丽娜,向大位,等.冰片及石菖蒲促进羟基红花黄色素A透过血脑屏障的实验研究[J].中草药,2011,42(4)：734-737.
[21]唐勇,漆伟,叶承莉,等.补阳还五汤加麝香辅助治疗脊髓损伤临床研究[J].中医学报,2013,28(2)：288-290.
[22]喻斌,阮鸣,董小平,等.不同时隔时间冰片处理对大鼠栀子苷脑靶效应的影响[J].中国药理学通报,2012,28(6)：862-866.
[23]冯宏业,葛朝丽.冰片对癫痫患者血清及脑脊液卡马西平药物浓度的作用[J].海南医学,2005,16(6)：11-12.
[24]吴珊,王凌.石菖蒲促进卡马西平透过血脑屏障的实验研究[J].福建医药杂志,2013,35(5)：67-84.
[25]陈瑞玲,赵志刚,张星虎,等.冰片对丙戊酸钠透过血脑屏障的影响[J].中国康复理论与实践,2007,13(2)：151-153.
[26]倪彩霞,曾南,汤奇.芳香开窍药对正常小鼠血脑屏障通透性的影响[J].江苏中医药,2011,43(2)：88-89.
[27]魏宇宁,刘萍,何新荣,等.微透析法研究冰片对头孢曲松在大鼠脑纹状体中含量的影响[J].中国中药杂志,2010,35(19)：2605-2608.
[28]王丹丹,王建,彭颖,等.四味芳香开窍药的挥发性成分对缺血缺氧PC12细胞及细胞内Ca2+的影响[J].西安交通大学学报(医学版),2012,33(3)：370-373.
[29]倪彩霞,曾南,许福会,等.芳香开窍药对脑缺血再灌注损伤大鼠血脑屏障影响的实验研究[J].中国中药杂志,2011,36(18)：2562-2566.
[30]杨洋,王世祥,房敏峰,等.安息香醛、香草醛和β-细辛醚对P-糖蛋白功能的影响[J].中成药,2012,34(7)：1364-1366.
[31]朱国栋.冰片开放血脑屏障及通过P糖蛋白介导的机制研究[D].广州：广州医学院,2009：32.
[32]王虹.石菖蒲活性成分醒脑开窍、透过血脑屏障作用机制研究[D].北京：中国人民解放军军医进修学院,2007：49.
[33]周金雯.天然冰片、合成冰片及薄荷脑对P-糖蛋白的影响及其机制研究[D].南京：南京师范大学,2011：48.
[34]占宏伟,刘洪彪,叶小娟,等.冰片对P-糖蛋白影响的99mTc-MIBI显像研究[J].中国现代药物应用,2012,6(22)：1-3.
[35]段美美,曾武,陈浩,等.天然冰片对顺铂在C6脑胶质瘤模型大鼠体内的药动学及 脑组织分布的影响[J].中药药理与临床,2013,29(5)：24-27.
[36]陈振振,杜守颖,陆洋,等.艾片与麝香酮芳香开窍作用机制研究[J].中药材2014,37(3)：462-466.
[37]洪艳丽,蒋凤荣.麝香酮对氧化应激损伤人血管内皮细胞凋亡的影响[J].中华中医药杂志,2011,26(9)：2178-2180.
[38]陈艳明,王宁生.冰片对血脑屏障体外模型细胞紧密连接和细胞吞饮囊泡的影响[J].中国中西医结合杂志,2004,24(7)：632-634.
[39]刘煜德,孙丹邈,黄小洵,等.冰片对BMSCs透过血脑屏障的影响[J].亚太传统医药,2007,3(7)：46-48.
[40]刘亚敏,赵光峰,夏鑫华,等.麝香配伍冰片对缺血再灌注损伤后血脑屏障的影响[J].北京中医药,2009,28(6)：459-462.
[41]梁雪冰,吴杰,赵国平,等.运用HPLC和GC-MS研究开心散有效抗抑郁成分大鼠吸收情况[J].辽宁中医杂志,2013,40(2)：365-367.
[42]陈怡君,周文斌,赵宝全,等.麝香酮对斑马鱼血脑屏障及其组成蛋白claudin5a的影响//第九届全国天然有机化学学术会议论文集[C].海南海口：[出版社不详],2012：132.
[43]葛朝丽,韩漫夫,白润涛,等.冰片促进血脑屏障开放的超微结构研究[J].中西医结合心脑血管病杂志,2008,6(10)：1183-1185.
[44]胡园,袁默,刘屏,等.石菖蒲对血脑屏障超微结构及通透性的影响[J].中国中药杂志,2009,34(3)：349-351.
[45]李荣伟,姚丽梅,宓穗卿,等.冰片对大鼠下丘脑组胺、5-羟色胺含量的影响[J].中药材,2004,27(12)：937-939.
[46]李伟荣,姚丽梅,宓穗卿,等.冰片开放血脑屏障作用与组胺和5-羟色胺的关系[J].中国临床康复,2006,10(3)：167-169.
[47]谢婷婷,王虹,刘屏,等.中药石菖蒲对脑内单胺类神经递质5-羟色胺水平的影响[J].中国药物应用与监测,2007,(3)：15-17.
[48]陈长才,柯以铨,徐如祥.5-羟色胺在脑微血管中的变化与血脑屏障的关系[J].中华医学杂志,1997,77(4)：298-299.
[49]李涛.汪受传治疗小儿癫痫经验[J].中医杂志,2013,54(17)：1458-1460.
[50]何迎春.朱良春治痰经验浅析[J].中医杂志,2012,53(21)：1812-1813.
[51]刘绪银.化痰熄风、化瘀通窍治疗癫痫—国医大师张学文治疗脑病经验之五[J].中医临床研究,2011,3(19)：23.
[52]田洪亮,朱万青,黄伟,等.王雪峰教授豁痰健脾论治小儿癫痫[J].中国中西医结合儿科学,2012,4(6)：485-486.
[53]司富春,宋雪杰,李洁,等.癫痫证候和方药分布规律文献分析[J].中医杂志,2014,55(6)： 508-512.
[54]王越,刘金民,李淑芳,等.癫痫中医证型及证候要素分布规律的文献研究[J].环球中医药,2013,6(1)：16-19.
[55]黄小波,张国君,陈文强,等.难治性癫痫中医证候聚类分析[J].中国中医药信息杂志,2011,18(12)：24-26.
[56]黄小波,张国君,王晓飞,等.难治性癫痫中医证候的判别分析[J].中华中医药杂志,2012,27(12)：3072-3076.
[57]李振光,王净净.从“痰瘀同治”论治难治性癫痫[J].中医学报,2013,28(181)：832-834.
[58]李伟,胡凯文,苏伟,等.浙贝母散剂逆转急性白血病多药耐药的临床研究[J].北京中医药大学学报,2004,27(1)：63-65.
[59]李泽慧,安超,胡凯文,等.浙贝母总碱对人肺腺癌A549/顺铂细胞耐药性的逆转作用[J].中国药理学与毒理学杂志,2013,27(3)：315-320.
[60]王耘,胡凯文,安超.贝母素乙联合氨苄西林舒巴坦抗耐药菌感染的体内实验研究[J].中华中医药杂志,2010,25(12)：2010-2013.
[61]顾政一,张裴,聂勇战,等.5种生物碱胃癌多药耐药逆转剂的筛选及机制研究[J].中草药,2012,43(6)：1151-1156.
[62]招丽君,廖正根,梁新丽,等Caco-2细胞单层模型研究葛根提取物中葛根素转运机制及白芷提取物对其转运的影响[J].中国药学杂志,2012,47(20)：1638-1642.
[63]梁新丽,招丽君,廖正根,等Caco-2细胞模型研究白芷提取物对P-糖蛋白功能的影响[J].中国医院药学杂志,2012,32(22)：1781-1785.
[64]祝婧云,梁新丽,王光发,等.白芷提取物对黄芩活性成分黄芩苷的吸收促进作用[J].药学学报,2011,46(2)：232-237.
[65]王姝麟,李霞,王小宁,等.欧白芷素对K562/A02细胞阿霉素耐药的逆转作用[J].中国天然药物,2011,9(2)：146-150.
[66]姜登钊.中药百部归经的研究及其在海洋中药研发中的应用[J].青岛：中国海洋大学,2010：73.
[67]周震,宋宛珊,王占奎,等.化痰通络法对急性脑梗死大鼠溶栓后血脑屏障通透性及海马内皮细胞超微结构的影响[J].中华行为医学与脑科学杂志,2012,21(6)：508-511.
[68]张玉莲,周震,宋宛珊,等.化痰通络方对急性脑梗死大鼠溶栓后血脑屏障相关构成蛋白表达的影响[J].中医杂志,2013,54(24)：2128-2134.
[69]侯文.基于“痰瘀同治”的健脑益智胶囊对颅脑损伤大鼠脑组织微循环的影响[D].西安：陕西中医学院,2011：25.
[70]郜菲.益气活血化痰通络法对脑缺血小鼠海马组织MMP-9、TIMP-1表达的影响[D].石家庄：河北医科大学,2011：34.
[71]韩为.益气活血化痰法对脑缺血再灌注大鼠葡萄糖转蛋白、细胞间粘附分子-1表达的 影响[D].北京：北京中医药大学,2006：84.
[72]樊帆,丁晶,张倩倩,等.癫痫持续状态大鼠脑水肿及血脑屏障破坏的动态观察[J].中国临床神经科学,2013,21(5)：498-503.
[73]陈基焱,黄吉春,高然,等.癫痫大鼠血脑屏障超微结构改变及妥泰的保护作用[J].解剖学报,2008,39(4)：498-501.
[74]古艳婷,马永刚,王明正,等.半夏生物总碱对癫痫大鼠海马氨基酸含量和GABAA受体mRNA表达的影响[J].中国药学(英文版),2009,18：252-256.
[75]杨蓉,王明正,成银霞.半夏等6中中药超临界CO2乙醇萃取物对青霉素诱发大鼠痫性放电和海马区相关递质含量的比较研究[J].中国中医基础医学杂志2013,19(5)：507-510,554.
[76]杨蓉,王明正,成银霞.天南星超临界CO2乙醇萃取抗惊厥作用的实验研究[J].中西医结合心脑血管病杂志,2013,11(6)：736-738.
[77]孔美珠.癫痫发作期中医证素分布规律的研究[D].福州：福建中医药大学,2013：14.
[78]刘永旭.癫痫从肝风痰瘀论治—闫也教授临床经验总结[D].沈阳：辽宁中医药大学,2011：18.
[79]谢炜,史国军,李长征,等.柴胡疏肝汤对难治性癫痫大鼠脑电图及多药耐药蛋白P-糖蛋白表达的影响[J].中国实验方剂学杂志,2011,17(3)：128-131.
[80]谢炜,陈伟军,孟春想,等.柴胡皂苷a对难治性癫痫大鼠多药耐药蛋白P-糖蛋白表达的影响[J].中国实验方剂学杂志,2013,19(9)：229-232.
[81]杨李华.钩藤生物总碱对耐药惊厥大鼠脑内P-gp基因表达的影响[D].太原：山西医科大学,2007：22.
[82]王永辉.柴胡总皂苷对小鼠部分药物代谢酶及P-糖蛋白的影响[D].广州：广州中医药大学,2012：54.
[83]冯丽敏,张娴,赵瑞芝.醋柴胡小分子水溶性部位抑制HEK293-Pgp细胞中P糖蛋白的外排功能[J].中国药理学通报,2013,29(12)：1684-1688.
[84]李淑雯,胡志方.香附醋制前后对Caco-2细胞P-糖蛋白功能和表达的影响[J].中国实验方剂学杂志,2013,19(16)：217-219.
[85]陈彦,王晋艳,辛然,等.柴胡皂苷对芍药苷在Caco-2细胞模型中吸收转运的影响[J].中国中药杂志,2012,37(12)：1850-1854.
[86]王晓丹,曾苏.天麻素在Caco-2细胞及Bcap37\Bcap37/MDR1细胞模型中的转运和摄取[J].药学学报(英文版),2010,45(12)：1497-1502.
[87]王俏.天麻素和天麻苷元的体内外代谢和脑靶向性研究[D].杭州：浙江大学,2007：94-95.
[88]徐虹.当归提取物与P-糖蛋白相互作用的初步研究[D].长沙：中南大学,2010：42.
[89]谢炜,李长征,鲍勇,等.戊四氮慢性点燃大鼠海马谷氨酸、γ-氨基丁酸阳性细胞变 化及柴胡总皂甙的干预作用[J].南方医科大学学报,2006,26(8)：1132-1135.
[90]谢炜,于云红,赵云燕.柴胡疏肝汤对戊四氮慢性点燃大鼠不同脑区兴奋性的影响[J].中国中药杂志,2010,35(12)：1619-1622.
[91]陈小银,田礼义.天麻素对戊四氮致痫大鼠海马氨基酸递质的影响[J].天津中医药,2009,26(6)：476-478.
[92]姚小卫.红藻酸癫痫大鼠不同脑区的5-HT含量变化[J].湖北中医学院学报,2009,11(5)：21-22.
[93]吴浪龙,李祖荣.不同脑区突触体内单胺类递质水平与惊厥发作和症状严重程度的相关性研究[J].中国康复理论与实践,2011,17(6)：546-548.
[94]吕晓钗,黄华品,林碗挥,等.脑内5-羟色胺减少对致痫大鼠癫痫发作及学习记忆的影响[J].中国应用生理学杂志,2012,28(3)：210-213,+1.
[95]Merlet I, Ostrowsky K, Costes N, et al.5-HT1A receptor binding and intracerebral activity in temporal lobe epilepsy:an [18F] MPPF-PET study[J]. Brain,2004,127 (Pt4):900-913.
[96]Hasler G, Bonwetsch R, Giovacchini C, et al.5-HT1A receptor binding in temporal lobe epilepsy patients with and without major depression[J]. Biol Psychiatry,2007,62(11): 1258-1264.
[97]郭长江,李亚军.单胺类神经递质在大鼠癫痫发作心脏损伤中的作用[J].陕西医学杂志,2008,37(3)：289-291.
[98]李娜,林卫红,营原秀贤.颞叶癫痫患者的心血管功能变化及相关因素分析[J].中风与神经疾病杂志,2009,26(2)：205-207.
[99]陶琳,孙美珍,杨萍,等.5-HT1A受体对癫痫伴发抑郁的影响及神经保护作用[J].中西医结合心脑血管病杂志,2011,9(6)：723-726.
[100]李琼,孙美珍,杨萍.5-羟色胺1A受体激动剂8-OH-DPAT对癫痫合并抑郁大鼠的干预作用及其机制研究[J].临床神经病学杂志,2013,26(3)：206-209.
[101]郑慧杰,舒友生,王开颜.5-羟色胺能对嗅海马联合皮层癫痫样放电的影响//第五届CAAE国际癫痫论坛会议论文集[C].重庆：[出版社不详],2013.
[102]高国丽,车光升,姜源,等.人参、天麻等复方总提取物对血管性痴呆大鼠脑组织单胺递质含量的影响[J].中国临床康复,2006,10(19)：182-183,186.
[103]周本宏,李小军,冯琪,等.天麻醇提取物对小鼠的抗抑郁作用[J].中国医院药学杂志,2007,27(11)：1525-1528.
[104]戈宏.柴胡皂苷抗抑郁作用及其机制的研究[D].长春：吉林大学,2010.
[105]崔广智,金树梅.芍药苷对强迫游泳小鼠脑内单胺递质的影响[J].天津中医药大学学报,2012,31(2)：83-84.
[106]周中流,刘永辉.香附提取物的抗抑郁或性及其作用机制研究[J].中国实验方剂学杂志, 2012,18(7)：191-193.
[107]王永志,杜仪,韩玉,等.柴胡疏肝散对抑郁症大鼠海马神经递质含量的影响[J].北京中医药,2014,33(1)：50-53.
[108]白海侠.从痰瘀论治癫痫的机理探讨[J].中医药导报,2012,18(5)：96-98.
[109]黄世敬,王永炎.癫痫虚气留滞病机探讨[J].世界中西医结合杂志,2013,8(6)：541-543,551.
[110]蔡宇,余绍蕾,陈冰.中药活性成分逆转K562/ADM耐药性聚类模糊研究[J].中国药学杂志,2006,41(13)：971-973.
[111]渡边由香(日).大黄甘草汤及其组成生药对P-谈干白的抑制作用//日本药学会第125次年会论文摘要[J].国际中医药杂志,2006,28(1)：48.
[112]贺兼斌,廖慧中,张贻秋,等.人参皂苷Rg3对小鼠肺腺癌多药耐药的逆转作用[J].实用肿瘤杂志,2012,27(4)：373-377.
[113]徐晓军,石淑文,汤永民,等.人参皂苷Rh2抗白血病多药耐药细胞K562/VCR作用研究[J].中草药,2010,41(7)：1131-1135.
[114]周方,许红梅.大黄素对肝内胆汁淤积大鼠P-gp表达的影响[J].中国中药杂志,2010,35(7)：908-911.
[115]宋娟,刘晓磊,何娟,等.川芎嗪和人参皂苷Rgl对Caco-2细胞P-糖蛋白功能和表达的影响[J].中国药学杂志,2008,43(13)：987-991.
[116]萨础拉,吕航,姜艳艳,等.三皂苷在大鼠外翻肠囊中的吸收及与P-糖蛋白相互作用研究[J].北京中医药大学学报,2011,34(12)：836-842.
[117]张艳,王平,王进荣,等.在体单向肠灌流模型研究大黄素的大鼠肠吸收特性[J].中药新药与临床药理,2012,23(3)：286-290.
[118]杨力,王晓娟,李洁,等.三七总皂苷对脑缺血再灌注大鼠脑内P-gp表达的影响[J].中国临床解剖学杂志,2013,31(4)：94-96.
[119]谢桂.大黄对脑出血大鼠脑内occludin mRNA表达的影响[D].长沙：中南大学,2010：16.
[120]李玉芳,刘坤,杨智航,等.川芎嗪对大鼠脑缺血再灌注后occludin表达的影响[J].中国公共卫生,2013,29(11)：1635-1637.
[121]刘坤,姚阳.水蛭素对大鼠脑出血后血脑屏障通透性和紧密连接相关蛋白claudin-5表达的作用[J].沈阳医学院学报,2011,13(3)：137-139.
[122]李玉芳,刘坤,倪月秋,等.川芎嗪对大鼠脑缺血再灌注后血脑屏障的保护作用及Claudin-5表达的影响[J].中国医科大学学报,2013,42(6)：511-514.
[123]彭璠.大黄对脑出血大鼠闭锁小带蛋白-1作用的研究[D].长沙：中南大学,2010：19.
[124]刘曾旭,余庆,王向东,等.复方丹参对严重烫伤大鼠血脑屏障的保护作用[J].中国临床解剖学杂志,2011,29(5)：565-567.
[125]朱海燕,高永红,吴爱明,等.三七总皂苷对铝暴露脑微血管内皮细胞胞质紧密黏连蛋白1表达的影响[J].中国中医药信息杂志,2012,19(9)：36-39.
[126]朱海燕,高永红,马涛,等.三七总皂苷对铝暴露体外血脑屏障通透性的影响[J].中西医结合心脑血管病杂志,2011,9(11)：1359-1361.
[127]陆莹,罗亚非,范瑞娟.当归补血汤对大鼠局灶性脑缺血再灌注血-脑屏障和大脑皮质神经元的影响[J].神经解剖学杂志,2013,29(3)：301-305.
[128]唐宇平,蔡定芳,刘军,等.大黄改善急性脑出血大鼠血脑屏障损伤的水通道蛋白-4机理研究[J].中国中西医结合杂志,2006,26(2)：152-156.
[129]王晓红.丹参酮、血塞通对TNF-a诱导表达的影响及其机制研究[D].北京：北京中医药大学,2013：54.
[130]李建生,刘敬霞,孙捷,等.大黄苷元对骨髓间充质干细胞移植脑缺血大鼠血脑屏障的作用与机制[J].中国药理学通报,2008,24(12)：1628-1633.
[131]李建生,刘敬霞,孙捷,等.大黄苷元对骨髓间充质干细胞移植脑缺血大鼠基质金属蛋白酶的影响[J].中西医结合学报,2008,6(8)：810-816.
[132]李长栋,荔志云,白海,等.大黄素甲醚联合脐带间充质干细胞移植对创伤性脑损伤大鼠MMP-9和TIMP-1蛋白酶的影响[J].创伤外科杂志,2013,15(4)：306-309.
[133]李浩,张多斌,吴岚,等.丹参酮ⅡA对脑缺血再灌注损伤大鼠磷酸化p38MAPK和MMP-9表达及细胞凋亡的影响[J].中风与神经疾病杂志,2013,30(3)：229-233.
[134]唐超.丹参酮ⅡA对小鼠脑血管内皮细胞内皮素系统的影响[D].沈阳：中国医科大学,2008：3-4.
[135]同病异治对戊四氮点燃大鼠海马区谷氨酸代谢通路的影响[J].中国中西医结合杂志,2013,33(1)：95-99.
[1]李世绰,郑晓瑛,吴立文.中国癫痫预防与控制绿皮书[M].北京：北京大学出版社,2009：2.
[2]孟红梅,李娜,崔俐,等.吉林省部分农村地区癫痫流行病学调查[J].中风与神经疾病杂志,2010,27(12)：1108.
[3]Kwan P, Arzimanoglou A, Berg AT, et al. Definition of drug resistant epilepsy. Consensus proposal by the ad hoc Task Force of the ILAE Commission on Therapeutic Strategies [J]. Epilepsia,2010,51(6):1069-1077.
[4]Kwan P, Schachter SC, Brodie MJ. Drug-Resistant Epilepsy[J]. N Engl J Med,2011,365: 919-926.
[5]Feldmann M, Asselin MC, Liu J, et al. P-glycoprotein expression and function in patients with temporal lobe epilepsy:a case-control study[J]. The Lancet Neurology,2013, 12(8):777-785.
[6]郑香春,李淑芳,刘金民.柴贝止痫汤单药及合并用药治疗难治性癫痫临床观察[J].天津中医药,2012,29(3)：224-226.
[7]李卫红,青雪梅,华茜,等.大鼠脑微血管内皮细胞条件培养液对皮层神经元活性的影响以及通络救脑注射液的干预作用[J].中华中医药杂志,2006,21(6)：334-337.
[8]Helms HC, Madelung R, Waagepetersen HS, et al. In vitro evidence for the brain glutamate efflux hypothesis:brain endothelial cells cocultured with astrocytes display a polarized brain-blood transport of glutamate [J]. GLIA,2012,60:882-893.
[9]Bernas MJ, Cardoso FL, Daley SK, et al. Establishment of primary cultures of human brain microvascular endothelial cells:a new and simplified menthod to obtain cells for an in vitro model of the blood-brain barrier[J]. Nat Protoc,2010,5(7):1262-1272.
[10]Li GL, Simon MJ, Cancel LM, et al. Permeability of endothelial and astrocyte cocultures: in vitro blood-brain barrier models for drug delivery studies[J]. Annals of Biomedical Engineering,2010,38(8):2499-2511.
[11]Wolburg H, Noell S, Mack A, et al. Brain endothelial cells and the glio-vascular complex[J]. Cell Tissue Res,2009,335:75-96.
[12]Ge S, Pachter JS. Isolation and culture of microvascular endothelial cells from murine spinal cord[J]. JNeuroimmunol,2006,177:209-214.
[13]Hatherell K, Couraud PO, Romero IA, et al. Development of a three-dimensional, all-human in vitro model of the blood-brain barrier using mono-, co-, and tri-cultivation transwell models[J]. Journal of Neurosicence Methods,2011,199(2):223-229.
[14]Kuo YC, Lu CH. Effect of human astrocytes on the characterisstics of human brain-microvascular endothelial cells in the blood-brian barrier[J]. Colloids and Surfaces B:Biointerfaces,2011,86(1):225-231.
[15]Thanabalasundaram G, Schneidewind J, Pieper C, et al. The impact of pericytes on the blood-brian barrier integrity depends critically on the pericyte differentitation stage[J].The International Journal of Biochemistry & Cell Biology,2011,43(9):1284-1293.
[16]Thanabalasundaram G, Pieper C, Lischper M, et al. Regulation of the blood-brain integrity by pericytes via matrix metalloproteinases mediated activation of vascular endothelial growth factor in vitro[J]. Brain Research,2010,1347:1-10.
[17]Haseloff RF, Blasig IE, Bauer HC, et al. In search of the astrocytic factor(s) modulating blood-brain barrier functions in brain capillary endothelial cells in vitro[J]. Cellular and Molecular Neurobiology,2005,25(1):25-39.
[18]王喜军.中药血清药物化学的研究动态及发展趋势[J].中国中药杂志,2006,31(10)：789-791.
[19]王洪武,倪青,林兰.中药含药血清的研究进展及其在中医学中的应用[J].北京中医药,2008,27(9)：698-701.
[20]王国佐.血清药理学方法在中药研究中的进展[J].湖南中医药大学学报,2007,27(3)：78-80.
[21]贺石林,葛金文,贺蓉,等.质疑血清药理学,加强多层次半体内实验研究[J].中国药理学通报,2005,21(3)：277-279.
[22]葛金文,朱慧斌,王宇红,等.关于中药血清药理学方法的杂思考[J].世界科学技术—中医药现代化,2008,10(6)：16-22.
[23]韩笑,刘建勋,林成仁.血清药理学关键问题的存疑与讨论[J].中药药理与临床,2009,25(2)：122-124.
[24]陈赐慧,花宝金.关于中药血清药理学实验的几个问题和探讨[J].中华中医药学刊,2013,31(1)：46-48.
[25]林圆圆,杜武勋,张少强,等.基于血清药理学的中药复方时效关系研究[J].中医杂志,2013,54(14)：1175-1178.
[26]Loscher W, Luna C, Romermann K, et al. Do ATP-binding cassette transporters cause pharmacoresistance in epilepsy? Problems and approaches in determining which anti-epileptic drugs are affected[J]. Curr.Pharm.Des,2011,17:2808-2828.
[27]Zhang C, Kwan P, Zuo Z, et al. The transport of antiepileptic drugs by P-glycoprotein[J]. Adv.Drug Delivery Rev,2012,64:930-942.
[28]Loscher W. Role of drug efflux transporters in the brain for drug disposition and treatment of brain diseases[J]. Prog Neurobiol,2005,76:22-76.
[29]Luna-Tortos C, Fedrowitz M, Loscher W. Several major antiepileptic drugs are substrates for human P-glycoprotein[J]. Neuropharmacology,2008,55(8):1364-1375.
[30]Bauer B, Hartz A.M.S, Pekcec A, et al. Seizure-induced up-regulation of P-glycoprotein at the blood-brain barrier through glutamate and cyclooxygenase-2 signaling[J]. Mol Pharmacol,2008,73:1444-1453.
[31]刘金民,江涛.中医癫痫病证诊治标准化的思考[J].中西医结合学报,2006,4(6)：572-574.
[32]李淑芳.颞叶癫痫中医证候研究及柴贝止痫汤对癫痫大鼠GABAARal、 NMDAR1表达的影响[D].北京：北京中医药大学,2009.
[33]谢炜,陈伟军,孟春想,等.柴胡皂苷a对难治性癫痫大鼠多药耐药蛋白P-糖蛋白表达的影响[J].中国实验方剂学杂志,2013,19(9)：229-232.
[34]王俏,陈国神.天麻苷元大鼠鼻腔和静脉注射给药的脑药动学研究[J].中国新药杂志,2010,19(8)：708-712.
[35]胡园,袁默,刘屏,等.石菖蒲对血脑屏障超微结构及通透性的影响[J].中国中药杂志,2009,34(3)：349-351.
[36]李泽慧,安超,胡凯文,等.浙贝母总生物碱对人肺腺癌A549/顺铂细胞耐药性的逆转作用[J].中国药理学与毒理学杂志,2013,27(3)：315-320.
[37]杨洋,王世祥,房敏峰,等.安息香醛、香草醛和p-细辛醚对P-糖蛋白功能的影响[J].中成药,2012,34(7)：1364-1366.
[38]彭向前,冯玮,张文会.半夏醇提取液逆转多药耐药细胞系K562/A02的耐药性[J].中国实验方剂学杂志,2012,18(18)：157-160.
[1]Mao QC, Unadkat JD. Role of the breast cancer resistance protein(ABCG2) in drug transport[J]. The AAPS Journal,2005,7(1):E118-133.
[2]李卫红,青雪梅,华茜,等.大鼠脑微血管内皮细胞条件培养液对皮层神经元活性的影响以及通络救脑注射液的干预作用[J].中华中医药杂志,2006,21(6)：334-337.
[3]Narang VS, Fraga C, Kumar N, et al. Dexamethasone increases expression and activity of multidrug resistance transporters at the rat blood-brain barrier[J]. Am J Physiol Cell Physiol,2008,295:C440-C450.
[4]Sukowati CHC, Rosso N, Pascut D, et al. Gene and functional up-regulation of the BCRP/ABCG2 transporter in hepatocellular carcinoma[J].BMC Gastroenterology,2012, 12:160.
[5]Liu JYW, Thom M, Catarino CB, et al. Neuropathology of the blood-brain barrier and pharmaco-resistance in human epilepsy [J]. Brain,2012,135:3115-3133.
[6]Englund G, Jacobson A, Rorsman F, et al. Efflux transporters in ulcerative colitis: decreased expression of BCRP(ABCG2) and Pgp(ABCB1)[J]. Inflamm Bowel Dis,2007, 13:291-297.
[7]Nakanishi H, Yonezawa A, Matsubara K, et al. Impact of P-glycoprotein and breast cancer resistance protein on the brain distribution of antiepileptic drugs in knockout mouse models[J]. European Journal of Pharmacology,2013,710(1-3):20-28.
[8]Li G, Simon MJ, Cancel LM, et al. Permeability of endothelial and astrocyte cocultures: In vitro blood-brain barrier models for drug delivery studies[J]. Annals of Biomedical Engineering,2010,38(8):2499-2511.
[9]赵康峰,王种,孔建,等.不同血脑屏障模型的建立及其功能特点[J].环境与健康杂志,2012,29(2)：127-130.
[10]Wilhelm I, Fazakas C, Krizbai I A. In vitro models of the blood-brain barrier[J]. Acta Neurobiol Exp,2011,71:113-128.
[11]Kliewer SA, Goodwin B, Willson TM. The nuclear pregnane X receptor:a key regulator of xenobiotic metabolism[J]. Endocr Rev,2002,23:687-702.
[12]Bauer B, Hartz AMS, Fricker G, et al. Pregnane X receptor up-regulation of P-glycoptrotein expression and transport function at the blood-brain barrier[J]. Mol Pharmacol,2004,66(3):413-419.
[13]Swales KE, Moore R, Truss NJ, et al. Pregnane X receptor regulates drug metabolism and transport in the vasculature and protects from oxidative stress[J]. Cardiovasc Res, 2012,93(4):674-681.
[14]Zhang YH, Lu M, Sun XR, et al. Expression and activity of P-glycoprotein elevated by dexamethasone in culture retinal pigment epithelium involve glucocorticoid receptor and pregnane X receptor[J]. IOVS,2012,53(7):3508-3515.
[15]Malekshah OM, Lage H, Bahrami AR, et al. PXR and NF-κB correlate with the inducing effects of IL-1(3 and TNF-a on ABCG2 expression in breast cancer cell lines[J]. European Journal of Pharmaceutical Sciences,2012,47(2):474-480.
[16]Mosaffa F, Kalalinia F, Lage H, et al. Pro-inflammatory cytokines interleukin-1p, interleukin6 and tumor necrosis factor-a alter the expression of ABCG2 in cervix and gastric cancer cells[J]. Mol Cell Biochem,2012,363:385-393.
[17]Das A, Wallace IV GC, Holmes C, et al. Hippocampal tissue of patients with refractory temporal lobe epilepsy is associated with astrocyte activation, inflammation, and altered expression of channels and receptors[J]. Neuroscience,2012,220:237-246.
[18]Lzzo JG, Wu X, Wu TT, et al. Therapy-induced expression of NF-kappa B portends poor prognosis in patients with localized esophageal cancer undergoing preoperative chemo-radiation[J]. Dis Esophagus,2009,22(2):127-132.
[19]Lee SH, Kim H, Hwang JH, et al. Breast cancer resistance protein expression is associated with early recurrence and decreased survival in resectable pancreatic cancer patients[J]. Pathology International,2012,62(3):167-175.
[1]Loscher W. Animal Models of intractable Epilepsy [J].Progress in Neurobiology,1991, 53:239-258.
[2]Aronica E, Gorter J A, Redeker S, et al. Localization of breast cancer resistance protein (BCRP) in microvessel endothelium of human control and epileptic brain[J]. Epilepsia, 2005,46(6):849-857.
[3]Van Vliet E A, Redeker S, Aronica E, et al. Expression of multidrug transporters MRP1, MRP2, and BCRP shortly after status epilepticus, during the latent period, and in chronic epileptic rats[J]. Epilepsia,2005,46(10):1569-1580.
[4]Kedersha NL,Rome LH. Isolation and characterization of a novel ribonucle protein particle:large structures contain a single species of small RNA [J]. Cell Biol,1986,103(3): 699-709.
[5]Suprenant KA. Vault ribonucleoprotein particles:sarcophagi, gondolas, or safety deposit boxes?[J].Biochemistry,2002,41(49):14447-14454.
[6]Kickhoefer VA,Vasu SK, Rome LH. Vaults are the answer,what is the question? [J].Trends Cell Biol,1996,6(5):174-178.
[7]Van Zon A, Mossink MH, Scheper RJ, et al The vault complex [J]. Cell Mol Life Sci,2003, 60(9):1828-1837.
[8]Rybarova S, Batekova M,Hodoroval L, et al. Immunohistochemical detection of LRP protein in the normal human lung[J]. Bratisl Lek Listy,2001,102(2):66-72.
[9]Scheper RJ, Broxteman HJ, Scheffer GL,et al. Overexpression of a Mr 110,000 vesicular protein in non-P-glycoprotein-mediated multidrug resistance[J].Cancer Res,1993,53(7): 1475-1479.
[10]Izpuierdo MA, Scheffer GL, Flens MJ,et al. Broad distribution of the multidrug resistance-related vault lung resistance protein in normal tissues and tumors[J].Am J Pathol,1996,148(3):877-887.
[11]Scheffer GL, Wijngaard PLJ, Fkens MJ, et al. The drug resistance-related protein LRP is the human major vault protein [J]. Nature Med,1995,1(6):578-582.
[12]Izquierdo MA, Vanderzee AG, Vermorken JB, et al. Drug resistance-associated marker LRP for response to chemotherapy and prognoses in advanced ovarian carcinoma[J]. J Nat Cancer Inst,1995,87(16):1230-1237.
[13]Aronica E, Gorter JA, Van vliet EA, et al. Overexpression of the human major vault protein in gangliogliomas[J].Epilepsia,2003,44(9):1166-1175.
[14]Fosang AJ, Last K, Gardiner P, et al. Development of a cleavage-site-specific monoclonal antibody for detecting metalloproteinase-derived aggrecan fragments:detection of franments in human synovial fluids[J].Biochem J,1995,310(ptl):337-343.
[15]Van vliet EA, Aronica E, Redeker S, et al. Expression and cellular distribution of major vault protein:A putative marker for pharmacoresistance in a rat model for temporal lobe epilepsy [J].Epilepsia,2004,45(12):1506-1516.
[16]Sisodiya SM, Martinian L, Scheffer G L, et al. Major Vault Protein,a Marker of Drug Resistance, Is Upregulated in Refractory Epilepsy[J] Epilepsia,2003,44(11):1388-1396.
[17]赵凤玲,孙佳红,张宝兰,等.补肾益气活血中药对大鼠缺血再灌注脑组织血管内皮生长因子表达和血脑屏障通透性的影响[J].中国医药导报,2013,10(2)：20-25.
[18]李净,周慧生,何玲,等.益气活血法对气虚血瘀脑缺血再灌注损伤大鼠血脑屏障通透性及ICAM-1、MMP-9/-2的影响[J].中国中医基础医学杂志,2012,18(5)：510-512.
[1]Eid T, Thomas MJ, Spencer D, et al. Loss of glutamine synthetase in the human epilepogenic hippocampus:possible mechanism for raised extracellular glutamate in mesial temporal lobe epilepsy[J]. The Lancet,2004,363(9402):28-37.
[2]Sarac S, Afzal S, Broholm H, et al. Excitatory amino acid transporters EAAT-1 and EAAT-2 in temporal lobe and hippocampus in intractable temporal lobe epilepsy[J]. APMIS;2009,117(4):291-301.
[3]Rogawski MA. AMPA receptors as a molecular target in epilepsy therapy[J]. Acta Neurologica Scandinavica,2013,127(s 197):9-18.
[4]Clasadonte J, Dong J, Hines DJ, et al. Astrocyte control of synaptic NMDA receptors contributes to the progressive development of temporal lobe epilepsy[J]. PNAS,2013, 110(43):17540-17545.
[5]张英丰,汪小根,吴阳,等.微透析技术进行药动学研究的发展趋势及局限性探讨[J].中国实验方剂学,2011,17(15)：270-273.
[6]王杰琼,张惠云.微透析技术结合色-质联用检测细胞外液神经递质研究进展[J].医学综述,2011,17(7)：1052-1055.
[7]王晔.CQM对三叉神经痛模型大鼠镇痛效应及其对脑内兴奋性氨基酸递质的影响[D].北京：中国中医科学院,2013：30-32.
[8]李鹏,张美玉,王丹巧,等.青藤碱对SSNI模型大鼠镇痛效应及脑内兴奋性氨基酸递质的影响[J].中国药理学通报,2012,28(10)：1365-1369.
[2]李世绰主编.中国癫痫预防与控制绿皮书[M].北京：北京大学出版社,2009：2.
[3]孟红梅,李娜,崔俐,等.吉林省部分农村地区癫痫流行病学调查[J].中风与神经疾病杂志,2010,27(12)：1108.
[4]Mohanraj R, Norrie J, Stephen LJ, et al. Mortality in adults with newly diagnosed and chronic epilepsy:a retrospective comparative study[J]. Lancet Neurol,2006,5:481-7.
[5]Lawn ND, Barnlet WR, Radhakrishnan K, et al. Injuries due to seizures in persons with epilepsy:a population based study[J]. Neurology,2004,63:1565-1570.
[6]McCagh J, Fisk JE, Baker GA. Epilepsy, psychosocial and cognitive functioning [J]. Epilepsy Res,2009,86:1-14.
[7]Kwan P, Brodie MJ. Early identification of refractory epilepsy [J]. N Engl J Med,2000, 342:314-319.
[8]吴逊,沈鼎烈.难治性癫痫[J].中华神经科杂志,1998,31：4.
[9]Kwan P, Arzimanoglou A, Berg AT, et al. Definition of drug resistant epilepsy:Consensus proposal by the ad hoc Task Force of the ILAE Commission on Therapeutic Strategies [J]. Epilepsia,2010,51 (6):1069-1077.
[10]Sillanp M, Schmidt D. Early seizure frequency and aetiology predict long-term medical outcome in childhood-onset epilepsy[J].Brain,2009,132:989-998.
[11]舒凯,陈旭,雷霆,等.难治性癫痫的规范化外科治疗[J/CD].中华临床医师杂志：电子版,2012,6(9)：2237-2275.
[12]陈光福,马启玲,贾少微,等.体外反搏对难治性癫痫患儿局灶性脑血流灌注的影响[J/CD].中华临床医师杂志电子版,2009,3(1)：140-143.
[13]Kwan P, Schachter SC, Brodie MJ. Drug-resistant epilepsy[J]. N Engl J Med,2011,365: 919-926.
[14]Rodriguez-Baeza A, Torre FR, Poca A, et al. Morphological features in human cortical brain micro vessels after head injury:a three-dimensional and immunocytochemical study [J]. Anat Rec A Discov Mol Cell Evol,2003,273(1):583-593.
[15]Pardridge WM. Blood-brain barrier drug targeting:the future of brain drug development [J].Mol Interv,2003,3(2):90-105,151.
[16]Hediger M.A., Clemencon B, Burrier R, et al. The ABCs of membrane transporters in health and disease(SLC series):introduction[J]. Molecular Aspects of Medicine,2013,34: 95-107.
[17]Murugesan N, Macdonald J, Ge S, et al. Probing the CNS microvascular endothelium by immune-guided laser-capture microdissection coupled to quantitative RT-PCR[J]. Method Mol Biol,2011,755:385-394.
[18]Danbolt NC. Glutamate uptake[J]. Prog Neurobiol,2001,65(1):1-105.
[19]Grewer C, Gameiro A, Zhang Z, et al. Glutamate forward and reverse transport from molecular mechanism to transporter-mediated released after ischemia[J]. IUBMB Life, 2008,60(9):609-619.
[20]Kanai Y, Nussberger S, Romero MF, et al. Electrogenic properties of the epithelial and neuronal high affinity glutamate transporter[J]. JBiol Chem,1995,270(28):16561-16568.
[21]Zerangue N, Kavanaugh MP. Flux coupling in a neuronal glutamate transporter [J]. Nature, 1996,383(6601):634-637.
[22]Bailey CG, Ryan RM, Thoeng AD, et al. Loss-of-function mutations in the glutamate transporter SLC1A1 cause human dicarboxylic aminoaciduria[J]. J Clin Invest.,2011, 121(1):446-453.
[23]Benediktsson AM, Marrs GS, Tu JC, et al. Neuronal activity regulates glutamate transporter dynamics in developing astrocytes[J]. GLIA,2012,60:175-188.
[24]Cohen-Kashi-Malina K, Cooper I, Teichberg V. Mechanisms of glutamate efflux at the blood-brain barrier:involvement of glial cells[J]. Journal of Cerebral Blood Flow & Metabolism,2012,32:177-189.
[25]Huang YH, Bergles DE. Glutamate transporters bring competition to the synapse[J]. Curr Opin Neurobiol,2004,14:346-352.
[26]Tzingounis AV, Wadiche JI. Glutamate transporters:Confining runaway excitation by shaping synaptic transmission[J]. Nat Rev Neurosci,2007,8:935-947
[27]Magistretti PJ. Role of glutamate in neuron-glia metabolic coupling[J]. Am J Clin Nutr, 2009,90(suppl):875S-880S.
[28]Grewer C, Gameiro A, Rauen T. SLC1 glutamate transporters[J]. Eur J Physiol,2014, 466:3-24.
[29]Kanai Y, Clemencon B, Simonin A, et al. The SLC1 high-affinity glutamate and neutral amino acid transporter family[J]. Mol Aspects Med,2013,34(2-3):108-120.
[30]Liddelow S, Temple S, Mollgard K, et al. Molecular characterization of transport mechanisms at the developing mouse blood-CSF interface:a transcriptome approach [J].PLoS ONE,2012,7(3):e33554.
[31]Daneman R, Zhou L, Agalliu D, et al. The mouse blood-brain barrier transcriptome:a new resource for understanding the development and function of brain endothelial cells[J]. PLoS ONE,2010a,5(10):e13741.
[32]Holmseth S, Dehnes Y, Huang YH, et al. The density of EAAC1(EAAT3) glutamate transporters expressed by neurons in the mammalian CNS[J]. J Neurosci,2012,32:6000-6013.
[33]Aoyama K, Watabe M, Nakaki T. Modulation of neuronal glutathione synthesis by EAAC1 and its interacting protein GTRAP3-18[J]. Amino Acid,2012,42(1):163-169.
[34]Berman AE, Chan WY, Brennan AM, et al. N-acetylcysteine prevents loss of dopaminergic neurons in the EAAC1-/-mouse[J]. Ann Neurol,2011,69:509-520.
[35]Cao L, Li L, Zuo Z. N-acetylcysteine reverses existing cognitive impairment and increased oxidative stress in glutamate transporter type 3 deficient mice[J]. Neuroscience, 2012,220:85-89.
[36]Won SJ, Yoo BH, Brennan AM, et al. EAAC1 gene deletion alters zinc homeostasis and exacerbates neuronal injury after transient cerebral ischemia[J]. J Neurosci,2010,24:87-93.
[37]Bjornsen LP, Hadera MG, Zhou Y, et al. The GLT-1(EAAT2;slcla2) glutamate transporter is essential for glutamate homeostasis in the neocortex of the mouse[J]. Journal of Neurochemistry,2014,128(5):641-649.
[38]Schmitt A, Asan E, Puschel B, et al. Celluar and regional distribution of the glutamate tramsporter GLAST in the CNS of rats:nonradioactive in SituHybridization and comparative immunocytochemistry[J]. The Journal of Neuroscience,1997,17(1):1-10.
[39]Berger UV, Hediger MA. Distribution of the glutamate transporters GLT-1(SLC1 A2) and GLAST(SLC1 A3) in peripheral organs[J]. Anat Embryol,2006,211:595-606.
[40]Shin JW, Nguyen KTD, Pow D, et al. Distribution of glutamate transporter GLAST in membranes of cultured astrocytes in the presence of glutamate transport substrates and ATP[J]. Neurochem Res,2009,34:1758-1766.
[41]Martinez-Lozada Z, Guillem AM, Flores-Mendez M, et al. GLAST/EAAT1-induced Glutamine release via SNAT3 in Bergmann glial cells:evidence of a functional and physical coupling[J]. Journal of Neurochemistry,2013,125(4):545-554.
[42]Martinez-Lozada Z, Hernandez-Kelly LC, Aguilera J, et al. Signaling through EAAT-1/ GLAST in cultured Bergmann glial cells[J]. Neurochemistry International,2011,59(6): 871-879.
[43]Miyazaki T, Takasaki C, Watanabe M. Neural circuit development and plasticity shaped by glutamate transporters [J]. Molecular Imaging for Integrated Medical Therapy and Drug Development,,2010,207-221.
[44]Tsai M-G, Tanaka K, Overstreet-Wadiche L, et al. Neuronal glutamate transporters regulate glial excitatory transmission[J]. The Journal of Neuroscience,2012,32(5): 1528-1535.
[45]Schneider N, Cordeiro S, Machtens JP, et al. Functional properties of the retinal glutamate transporters GLT-1 and EAAT5[J]. The Journal of Biological Chemistry,2014, 289:1815-1824.
[46]Mueckler M, Makepeace C. Model of the exofacial sbustrate-binding site and helical folding of the human Glutl glucose transporter based on scanning mutagenesis[J]. Biochemistry,2009,48(25):5934-5942.
[47]Thorens B, Mueckler M.Glucose transporters in the 21st century[J]. Am J Physiol Endocrinol,2010,298(2):E141-145.
[48]Augustin R. The protein family of glucose transport facilitators:It's not only about glucose after all[J]. IUBMB Life,2010,62(5):315-333.
[49]Bibert S, Hess SK, Firsov D, et al. Mouse GLUT9:evidences for a urate uniporter[J].Am J Physiol Renal Physiol,2009,297(3):F612-619.
[50]Lee YC, Huang HY, Chang CJ, et al. Mitochondrial GLUT10 facilitates dehydroascorbic acid import and protects cells against oxidative stress:mechanistic insight into arterial tortuosity syndrome [J]. Hum Mol Genet,2010,19(19):3721-3733.
[51]Alexander SPH, Mathie A, Peters JA. Guide to receptors and channels(GRAC),5th edn[J]. Br J Pharmacol,2011,164(Suppl.1):S1-S324.
[52]Guo XL, Geng MY, Du GH. Glucose transporter 1, distribution in the brain and in neural disorders:its relationship with transport of neuroactive drugs through the blood-brain barrier[J]. Biochemical Genetics,2005,43(3/4):175-187.
[53]Uldry M, Ibberson M, Hosokawa M, et al.GLUT2 is a high affinity glucosamine transporter[J]. FEBS Lett,2002,524:199-203.
[54]Devraj K, Klinger ME, Myers RL, et al.GLUT-1 glucose transporters in the blood-brain barrier:differential phosphorylation[J]. J Neurosci Res,2011,89(12):1913-1925.
[55]Hayes J D, Pulford D J. The Glut athione S-Transferase Supergene Family:Regulation of GST and the Contribution of the lsoenzymes to Cancer Chemoprotection and Drug Resistance Part Ⅰ[J]. Critical reviews in biochemistry and molecular biology,1995,30(6): 445-520.
[56]Pardridge W M, Boado R J, Farrell C R. Brain-type glucose transporter (GLUT-1) is selectively localized to the blood-brain barrier. Studies with quantitative western blotting and in situ hybridization[J]. Journal of Biological Chemistry,1990,265(29):18035-18040.
[57]Russell R R, Bergeron R, Shulman G I, et al. Translocation of myocardial GLUT-4 and increased glucose uptake through activation of AMPK by AICAR[J]. American Journal of Physiology-Heart and Circulatory Physiology,1999,277(2):H643-H649.
[58]Hughes V A, Fiatarone M A, Fielding R A, et al. Exercise increases muscle GLUT-4 levels and insulin action in subjects with impaired glucose tolerance[J]. American Journal of Physiology-Endocrinology And Metabolism,1993,264(6):E855-E862.
[59]Megeney L A, Neufer P D, Dohm G L, et al. Effects of muscle activity and fiber composition on glucose transport and GLUT-4[J]. American Journal of Physiology-Endocrinology And Metabolism,1993,264(4):E583-E593.
[60]Beltran FA, Acuna AI, Miro MP, et al. Ascorbic acid-dependent GLUT3 inhibition is a critical step for switching neuronal metabolism[J]. Journal of Cellular Physiology,2011, 226(12):3286-3294.
[60]Carayannopoulos MO, Xiong FX, Jensen P, et al. GLUT3 gene expression is critical for embryonic growth, brain development and survival [J]. Molecular Genetics and Metablism,2014,online
[60]Brown K, Heller DS, Zamudio S, et al. Glucose transporter 3(GLUT3) protein expression in human placenta across gestation[J]. Placenta,2011,32(12):1041-1049.
[63]Scheffer I E. GLUT1 deficiency A glut of epilepsy phenotypes[J]. Neurology,2012,78(8): 524-525.
[64]Leary L D, Wang D, Nordli D R, et al. Seizure Characterization and Electroencepha-lographic Features in Glut-1 Deficiency Syndrome[J]. Epilepsia,2003,44(5):701-707.
[65]Hall GV, Stromstad M, Rasmussen P, et al. Blood lactate is an important energy source for the human brain[J]. Journal of Cerebral Blood Flow & Metabolism,2009.,29:1121-1129.
[66]Lutas A, Yellen G. The ketogenic diet:metabolic influences on brain excitability and epilepsy[J]. Trend in Neurosciences,2013,36(1):32-40.
[67]Simpson IA, Carruthers A, Vannucci SJ. Supply and demand in cerebral energy metabolism:the role of nutrient transporters [J]. Journal of Cerebral Blood Flow & Metabolism,2007,27:1766-1791.
[68]Dienel GA. Fueling and imaging brain activation[J].ASN Neruo,2012,4(5):e00093.
[69]Harris JJ, Jolivet R, Attwell D. Synaptic energy use and supply[J]. Neuro,2012,75(5): 762-777.
[70]Gandhi GK, Cruz NF, Ball KK, et al. Astrocytes are poised for lactate trafficking and release from activated rain and for supply of glucose to neurons[J]. Journal of Neurochemistry,2009,111:522-536.
[71]Rouach N, Koulakoff A, Abudara V, et al. Astroglial metabolic networks sustain hippocampal synaptic transmission[J]. Science,2008,332:1551-1555.
[72]Leroy C, Pierre K, Simpson I A, et al. Temporal changes in mRNA expression of the brain nutrient transporters in the lithium-pilocarpine model of epilepsy in the immature and adult rat[J]. Neurobiology of disease,2011,43(3):588-597.
[73]Hildebrand M S, Damiano J A, Mullen S A, et al. Glucose metabolism transporters and epilepsy:Only GLUT1 has an established role[J]. Epilepsia,2014.
[74]Gerhart D Z, Leino R L, Taylor W E, et al. GLUT1 and GLUT3 gene expression in gerbil brain following brief ischemia:an in situ hybridization study [J]. Molecular brain research, 1994,25(3):313-322.
[75]Simpson I A, Chundu K R, Davies-Hill T, et al. Decreased concentrations of GLUT1 and GLUT3 glucose transporters in the brains of patients with Alzheimer's disease [J]. Annals of neurology,1994,35(5):546-551.
[76]Gronlund K M, Gerhart D Z, Leino R L, et al. Chronic seizures increase glucose transporter abundance in rat brain[J]. Journal of Neuropathology & Experimental Neurology,1996,55(7):832-840.
[77]Ueno M, Nishi N, Chiba TNY, et al. Immunoreactivity of glucose transporter 5 is located in epithelial cells of the choroid plexus and ependymal cells[J]. Neuroscience,2014,260: 149-157.
[78]Page KA, Chan O, Arora J, et al. Effects of fructose vs glucose on regional cerebral blood flow in brain regions involved with appetite and reward pathways[J]. JAMA,2013,309(1): 63-70.
[79]Ibberson M, Riederer BM, Uldry M, et al. Immunolocalization of GLUTX1 in th testis and to specific brain areas and vasopressin-containing neurons[J]. Endocrinology,2002, 143(1):276-284.
[80]Gomez O, Romero A, Terrado J, et al. Differential expression of glucose transporter GLUT8 during mouse spermatogenesis[J]. Reprduction,2006,131:63-70.
[81]Gavlik V, Schmidt S, Scheepers A, et al. Targeted disruption of Slc2a8(GLUT8) reduces motility and mitochondrial potential of spermatozoa[J]. Mol.Membr.Biol,2008,25:224-235.
[82]Reagan LP, Rosell DR, Alves SE, et al. Glut8 glucose transporter is localized to excitatory and inhibitory neurons in the rat hippocampus [J]. Brain Res,2002,932:129-134.
[83]Membrez M, Hummler E, Beemann F, et al. GLUT8 is dispensable for embryonic development but influences hippocampal neurogenesis and heart function[J]. Mol Cell Biol,2006,26:4268-4276.
[84]Schmidt S, Joost HG, Schurmann A. GLUT8, the enigmatic intracellular hexose ransporter[J]. Am JPhysiol Endocrinol Metab,2009,296:E614-618.
[85]Mora F, Segovia G, Arco A, et al. Stress, neurotransmitters, corticosterone and body-brain intergration[J]. BRAIN RESEARCH,2012,1476:71-85.
[86]Jurcovicova J.Glucose transport in brain-effect of inflammation[J].Endocrine Regulations, 2014,48(1):35-48.
[87]Bourgeois F, Coady M J, Lapointe J Y. Determination of transport stoichiometry for two cation-coupled myo-inositol cotransporters:SMIT2 and HMIT[J]. The Journal of physiology,2005,563(2):333-343.
[88]Di Daniel E, Mok M H S, Mead E, et al. Evaluation of expression and function of the H+/myo-inositol transporter HMIT[J]. BMC cell biology,2009,10(1):54.
[89]Didaniel E, Kew J N, Maycox P R. Investigation of the H+-myo-inositol transporter (HMIT) as a neuronal regulator of phosphoinositide signalling[J]. Biochemical Society Transactions,2009,37(5):1139.
[90]Wood I S, Hunter L, Trayhurn P. Expression of Class III facilitative glucose transporter genes (GLUT-10 and GLUT-12) in mouse and human adipose tissues [J]. Biochemical and biophysical research communications,2003,308(1):43-49.
[91]D Serrano I, MB Ribeiro M, ARB Castanho M. A focus on glucose-mediated drug delivery to the central nervous system[J]. Mini reviews in medicinal chemistry,2012, 12(4):301-312.
[92]Broer S, Palacin M. The role of amino acid transporters in inherited and acquired diseases [J]. Biochem J,2011,436:193-211.
[93]Chen NH, Reith ME, Quick MW.Synaptic uptake and beyond:the sodium- and chloride-dependent neurotransmitter transporter family SLC6[J]. Pflugers Arch,2004, 447:519-531.
[94]Broer S. The SLC6 orphans are forming a family of amino acid transporters [J]. NeurochemInt,2006,48(6-7):559-567.
[95]Madsen KK, White HS, Schousboe A. Neuronal and non-neuronal GABA transporters as targets for antiepileptic drugs[J]. Pharmacol Ther,2010,125:394-401.
[96]Jin XT, Galvan A, Wichmann T, et al. Localization and function of GABA transporters GAT-1 and GAT-3 in the basal ganglia[J]. Fornt Syst Neurosic,2011,5:63.
[97]Kristensen AS, Andersen J, Jorgensen TN, et al. SLC6 neurotransmitter transporters: structure, function and regulation[J].Pharmacol Rev,2011,63:585-640.
[98]Schousboe A, Madsen KK, Barker-Haliski ML, et al. The GABA synapse as a target for antiepileptic drugs:a historical overview focused on GABA transporters [J]. Neurochemical Research,2014,3 doi:10.1007/sl 1064-014-1263-9.
[99]Pramod AB, Foster J, Carvelli L, et al. SLC6 transporters:structure, function, regulation, disease association and therapeutics [J]. Molecular Aspects of Medicine.,2013,34:197-219.
[100]Rudnick G, Kramer R, D.Blakely R, et al. The SLC6 transporters:perspectives on structure, functions, regulation, and models for transporter dysfunction[J]. Pflugers Arch-Eur J Physiol,2014,466:25-42.
[101]Plos TW, Noriega LG, Nomura M, et al. The bile acid membrane receptor TGR5 as an emerging target in metabolism and inflammation[J].J Hepatol,2011,54(6):1263-1272.
[102]Stieger B. The role of the sodium-taurocholate cotransporting polypeptide (NTCP) and of the bile salt export pump (BSEP) I physiology and pathophysiology of bile formation [J]. Handb.Exp.Pharmacol,2011,201:205-259.
[103]Akita H, H.Suzuki K, K.Ito S, et al. Characterization of bile acid transport mediated by multidrug resistance associated protein 2 and bile salt export pump [J]. Biochim Biophys Acta,2001,1511:7-16.
[104]D.Lee S, J.Thornton S, Sachs-Barrable K, et al. Evaluation of the contribution of the ATP binging cassette transporter, p-glycoprotein, to in vivo cholesterol homeostasis[J]. Mol. Pharmaceutics,2013,10(8):3203-3212.
[105]Telbisz A, Hegedus C, Baradi A, et al. Regulation of the function of the human ABCG2 multidrug transporter by cholesterol and bile acids:effects of mutations in potential substrate-and steroid-binging sites[J]. Drug Metab-Dispos,2014,42(4):575-585.
[106]Silva TC, E.Polli J, W.Swaan P. The solute carrier family 10 (SLC10):beyond bile acid transport [J]. Molecular Aspects of Medicine,,2013,,34:252-269.
[107]Burger S, Doring B, Hardt M, et al. Co-expression studies of the orphan carrier protein Slc10a4 and the vesicular carriers VAChT and VMAT2 in the rat central and peripheral nervous system[J].Neurosicence,2011,193:109-121.
[108]Halestrap AP, Meredith D. The SLC16 gene family-from monocardoxylate transporters (MCTs) to aromatic amino acid transporters and beyond[J]. Pflugers Arch.,2004,447: 619-628.
[109]Visser WE, Friesema EC, Visser TJ. Thyroid hormone transporters:the knowns and the unknowns[J]. Mol. Endocrinol,2011,25:1-14.
[110]Halestrap AP, C.Wilson M. The monocarboxylate transporter family-role and regulation [J]. IUBMB Life,2012,64(2):109-119.
[111]Halestrap AP. The monocardoxylate transporter family-structure and functional charac-terization[J]. IUBMU Life,2012.64(1):1-9.
[112]Cheng Z, Liu H, Yu N, et al. Hydrophilic anti-migraine triptans are substrates for OAPT1A2, a transporter expressed at human blood-brain barrier[J]. Xenobiotica,2012, 42(9):880-890.
[113]Bronger H, Konig J, Kopplow K, et al. ABCC drug efflux pumps and organic anion uptake transporters in human gliomas and the blood-tumor barrier[J]. Cancer Res,2005, 65:11419-11428.
[114]Alkemade A, Friesema EC, Kalsbeek A, et al. Expression of thyroid hormone trans-porters in the human hypothalamus[J]. JClin Endocrinol Metab,2011,96(6):E967-971.
[115]Roberts LM, Woodford K, Zhou M, et al. Expression of the thyroid hormone transporters monocarboxylate transporter-8 (SLC16A2) and organic ion transporter-14 (SLCO1C1) at the blood-brain barrier[J]. Endocrinology,2008,149(12):6251-6261.
[116]Fenner KS, Jones HM, Ullah M, et al. The evolution of the OATP hepatic uptake transport protein family in DMPK sciences:from obscure liver transporters to key determinants of hepatobiliary clearance[J]. Xenobiotica,2012,42(1):28-45.
[117]Obaidat A, Roth M, Hagenbuch B. The expression and function of organic anion transporting polypeptides in normal tissues and in cancer[J]. Annu Rev Pharmacol Toxicol,2012,52:135-151.
[118]Koepsell H. The SLC22 family with transporters of organic cations, anions and zwitterions[J] Molecular Aspects of Medicine.,2013,34:413-435.
[119]Cui M, Aras R, Christian WV, et al. The organic cation transporter-3 is a pivotal modulator of neurodegeneration in the nigrostriatal dopaminergic pathway [J]. Proc Natl Acad Sci U.S.A,2009,106:8043-8048.
[120]Gasnier B. The SLC32 transporter, a key protein for the synaptic release of inhibitory amino acids[J]. Pflugers Arch,2004,47(5):756-759.
[121]Pillai SM, Meredith D. SLC36A4 (hPAT4) is a high affinity amino acid transporter when expressed in Xenopus laevis oocytes[J]. JBiol Chem,2011,286(4):2455-2460.
[122]Sundberg BE, Waag R, Jacobsson JA, et al. The evolutionary history and tissue mapping of amino acid transporters belonging to solute carrier families SLC32, SLC36, and SLC38[J]. JMol Neruosci,2008,35(2):179-193.
[123]Schioth HB., Roshanbin S., Hagglund MG.A., et al. Evolutionary origin of amino acie transporter families SLC32, SLC36 and SLC38 and physiological, pathological and therapeutic aspects[J]. Molecular Aspects of Medicine,2013,34:571-581.
[124]Hagglund M.G., Sreedharan S., Nilsson VC.O, et al. Identification of SLC38A7 (SNAT7) protein as a glutamine transporter expressed in neurons[J]. J. Biol. Chem.,2011,286: 20500-20511.
[125]Traiffort E., O'Regan S., Ruat M., The choline transporter-like family SLC44:properties and roles in human diseases[J]. Molecular Aspects of Medicine,2013,34:646-654.
[126]Machova E., O'Regan S., Newcombe J., et al. Detection of choline transporter-like 1 protein CTL1 in neuroblastoma & glioma cells and in the CNS, and its role in choline uptake[J]. Journal of Neurochemistry,2009,110:1297-1309.
[127]Miller DS. Regulation of P-glycoprotein and other ABC drug transporters at the blood-brain barrier[J]. Trends Pharmacol Sci,2010,31(6):246-254.
[128]Mahringer A, Ott M, Reimold I, et al. The ABC of the blood-brain barrier-regulation of drug efflux pumps[J]. Current Pharmaceutical Design,2011,17(26):2762-2770(9).
[129]Luna-Tortos C, Fedrowitz M, Loscher W. Several major antiepileptic drugs are substrates for human P-glycoprotein[J]. Neuropharmacology,2008,55(8):1364-1375.
[130]Zhang C, Kwan P, Zuo Z, et al. The transporter of antiepileptic drugs by P-glycoprotein [J]. Adv Drug Deliv Rev,2012,64(10):930-942.
[131]Agarwal S, Hartz AM, Elmquist WF, et al. Breast cancer resistance and P-glycoprotein in brain cancer:two gatekeepers team up[J]. Curr Pharm Des,2011,17:2793-2802.
[132]Uchida Y, Ohtsuki S, Katsukura Y, et al. Quantitative targeted absolute proteomics of human blood-brain barrier transporters and receptors [J]. JNeurochem,2011,117:333-345.
[133]Agarwal S, Sane R, Gallardo JL, et al. Distribution of gefitinib to the brain is limited by P-glycoprotein (ABCB1) and breast cancer resistance protein (ABCG2)-mediated active efflux[J]. J Pharmacol Exp Ther,2010,334:147-155.
[134]Paspalas CD, Perley CC, Venkitaramani DV, et al. Major vault protein is expressed along the nucleus-neurite axis and associates with mRNAs in cortical neurons[J]. Cerebral Cortex,2009,19:1666-1677.
[135]Balan S, Iekshmi S, Radha K, et al. Major vault protein (MVP) gene polymorphisms and drug resistance in mesial temporal lobe epilepsy with hippocampal sclerosis[J]. Gene,2013,526(2):449-453.
[136]Liu B, Wang T, Wang L, et al. Up-regulation of major vault protein in the frontal cortex of patients with intractable frontal lobe epilepsy [J].Journal of the Neurological Science, 2011,308(1-2):88-93.
[137]Sisodiya SM, Marinian L, Scheffer GL, et al. Vascular colocalization of P-glycoprotein, multidrug-resistance associated protein1, breast cancer resistance protein and major vault protein in human epileptogenic pathologies[J]. Neuropathology and Applied Neurobi-ology,2006,32(1):51-63.
[138]Kovacs R, Raue C, Gabriel S, et al. Functional test of multidrug transporter activity in hippocampal-neocortical brain slices from epileptic patients[J]. Journal of Neuroscience Methods,2011,200(2):164-172.
[139]Wilhelm I, Fazakas C, Krizbai IA. In vitro models of the blood-brain barrier[J].Acta Neurobiol Exp(Wars),2011,71:113-128.
[140]Redzic Z. Molecular biology of the blood-brain and the blood-cerebrospinal fluid barriers:similarities and differences[J]. Fluids Barriers CNS,2011,8:3.
[141]Liddelow SA, Temple S, Mollgard K, et al. Molecular characterization of transport mechanisms at the developing mouse blood-CSF interface:a transcriptome approach[J]. PLoS One,2012,7:e33554.
[142]Cardoso FL, Brites D, Brito MA. Looking at the blood-brain barrier:molecular anatomy and possible investigation approaches[J].Brain Research Reviews,2010,64:328-363.
[143]Wolburg H, Lippoldt A. Tight junctions of the blood-brain barrier:development, composition and regulation[J]. Vascular Pharmacology,2002,323-337.
[144]Luissint AC, Artus C, Glacial F, et al. Tight junctions at the blood brain barrier: physiological architecture and disease-associated dysregulation[J]. Fluids and Barriers of the CNS,2012,9:23.
[145]Terry S, Nie M, Matter K, et al. Rho signaling and tight junction functions[J]. Physiology,2010,25:16-26.
[146]Lee HS, Namkoong K, Kim DH, et al. Hydrogen peroxide-induced alterations of tight junction proteins in bovine brain microvascular endothelial cells[J]. Microvascular Research,2004,68(3):231-238.
[147]Persidsky Y, Ramirez SH, Haorah J, et al. Blood-brain barrier:structural components and function under physiologic and pathologic conditions [J]. J Neuroimmune Pharmacol, 2006,1(3):223-236.
[148]Weiss N, Miller F, Cazaubon S, et al. The blood-brain barrier in brain homeostasis and neurological diseases[J]. Biochim Biophys Acta,2009,
[149]Engelhardt B, Ransohoff RM. Capture, crawl, cross:the T cell code to breach the blood-brain barriers[J]. Trends Immunol,2012,33:519-589.
[150]Hawkins BT, Abbruscato TJ, Egleton RD, et al. Nicotine increases in vivo blood-brain barrier permeability and alters cerebral microvascular tight junction protein distribution [J].Brain Res,2004,1027:48-58.
[151]Brown RC, Davis TP. Hypoxia/aglycemia alters expression of occludin and actin in brain endothelial cells[J]. Biochem Biophys Res Commun,2005,327:1114-1123.
[152]Dorfel MJ, Huber O. Modulation of tight junction structure and function by kinases and phosphatases targeting occludin[J] Journal of Biomedicine and Biotechnology,2012, 2012:807356.
[153]Itallie CMV, Fanning AS, Holmes J, et al. Occludin is required for cytokine-induced regulation of tight junction barriers[J]. Journal of Cell Science,2010,123(16):2844-2852.
[154]Buschmann MM, Shen L, Rajapakse H, et al. Occludin OCEL-domain interactions are required for maintenance and regulation of the tight junction barrier to macromolecular flux[J]. Mol. Biol. Cell,2013,24(19):3056-3068.
[155]Rao R. Occludin phosphorylation in regulation of epithelial tight junctions[J]. Ann of the New York Academy of Sciences,2009,1165:62-68.
[156]Itallie CMV, Anderson JM. Claudin interactions in and out of the tight junction[J]. Tissue Barrier,2013,1(3):e25247.
[157]Cording J, Berg J, Kading N, et al. In tight junctions, claudins regulate the interactions between occludin, tricellulin and marvelD3, which, inversely, modulate claudin oligomerization[J].Journal of Cell Science,2012,126:554-564.
[158]Kubota K, Furuse M, Sasaki H, et al. Ca2+-independent cell-adhesion activity of claudins, a family of integral membrane proteins localized at tight junctions[J].Curr Biol, 1999,9:1035-1038.
[159]Overgaard CE, Daugherty BL, Mitchell LA, et al. Claudins:control of barrier function and regulation in response to oxidant stress[J]. Antioxid. Redox signal,2011,15(5):1179-1193.
[160]Angelow S, Ahlstrom R, Yu ASL. Biology of Claudins[J]. Am J Physiol Renal Physiol, 2008,295:F867-F876.
[161]Gunzel D, Yu ASL. Claudins and the modulation of tight junction permeability [J].Physiol.Rev,2013,93:525-569.
[162]Nitta T, Hata M, Gotoh S, et al. Size-selective loosening of the blood-brain barrier in claudin-5-deficient mice[J]. J Cell Biol,2003,161:653-660.
[163]Jia W, Lu R, Martin TA, et al. The role of claudin-5 in blood-brain barrier (BBB) and brain metastases[J]. Mol Med Rep,2014,9(3):779-785.
[164]Fanning AS, Anderson JM. Zonula occludens-1 and -2 are cytosolic scaffolds that regulate the assembly of cellular junctions[J].Ann N YAcad Sci,2009,1165:113-120.
[165]Bauer H, Zweimueller-Mayer J, Steinbacher P, et al. The dual role of Zonula Occludens (ZO) proteins[J]. Journal of Biomedicine and Biotechnology,2010,2010:402593.
[166]Bauer B. Targeting regulation of ABC transporters at the blood-brain barrier to improve pharmacotherapy of CNS disorders[J]. International Drug Discovery,2010:76-79.
[167]Ghost C, Vikram P, Jorge GM, et al. Blood-brain barrier P450 enzymes and multidrug transporters in drug resistance:a synergistic role in neurological diseases[J]. Current Drug Metabolism,2011,12(8):742-749.
[168]Marchi N, Angelov L, Masaryk T, et al. Seizure-promoting effect of blood-brain barrier disruption[J].Epilepsia,2007,48(4):732-742.
[169]Pizzini FB, Farace P, Manganotti P, et al. Cerebral perfusion alterations in epileptic patients during peri-ictal and post-ictal phase:PASL vs DSC-MRI [J]. Magn Reson Imaging,2013,31(6):1001-1005.
[170]Bek S, Kasikci T, Koc G, et al. Cerebral vasomotor reactivity in epilepsy patients[J]. J Neurol,2010,257(5):833-838.
[171]Choy M, Wells JA, Thomas DL, et al. Cerebral blood flow changes during pilocarpine-induced status epilepticus activity in the rat hippocampus[J].Exp.Neurol,2010,225(1): 196-201.
[172]Badawy RA, Wogrin SL, Lai A, et al. Cortical excitability changes correlate with fluctuations in glucose levels in patients with epilepsy [J]. Epilepsy Behav,2013,27(3): 455-460.
[173]Akman CI, Ichise M, Olsavsky A, et al..Epilepsy duration impacts on brain glucose metabolism in temporal lobe epilepsy:results of voxel-based mapping[J].Epilepsy Behav,2010,17(3):373-380.
[174]Lutas A, Yellen G. The ketogenic diet:metabolic influences on brain excitability and epilepsy [J].Trends Neurosic,2013,36(1):32-40.
[175]Lee EM, Park GY, Im KC, et al. Changes in glucose metabolism and metabolites during the epileptogenic process in the lithium-pilocarpine model of epilepsy [J]. Epilepsia,2012, 53(5):860-869.
[176]Hildebrand MS, Damiano JA, Mullen SA, et al. Glucose metabolism transporters and epilepsy:only GLUT1 has an established role[J].Epilepsia,2014,55(2):e18-e21.
[177]Marin-Valencia I, Good LB, Ma Q, et al. Glutl deficiency (G1D):epilepsy and metabolic dysfunction in a mouse model of the most common human phenotype[J]. Neurobiology of Disease,2012,48(1):92-101.
[178]Vieker S, Schmitt J, Langler A, et al. Unusual sensitivity to steroid treatment in intractable childhood epilepsy suggests GLUT1 deficiency syndrome[J]. Neuropediatrics, 2012,43(5):275-278.
[179]Crino PB, Jin H, Shumate MD, et al. Increased expression of the neuronal glutamate transporter (EAAT3/EAAC1) in hippocampal and neocortical epilepsy [J]. Epilepsia, 2002,43(3):211-218.
[180]van der Hel WS, Verlinde SA, Meijer DH, et al. Hippocampal distribution of vesicular glutamate transporter 1 in patients with temporal lobe epilepsy[J]. Epilepsia,2009,50(7): 1717-1728.
[181]Liu B, Niu L, Shen MZ, et al. Decreased astroglial monocarboxylate transporter 4 expression in temporal lobe epilepsy[J]. Mol Neurobiol,2014,online.doi:10.1007/ sl2035-013-8619-z.
[182]Kong Q, Takahashi K, Schulte D, et al. Increased glutamate transporter EAAT2 expression reduces epileptogenic processes following pilocarpine-induced status epilepticus[J]. Neurobiol Dis.,2012,47(2):145-154.
[183]Lane MC,Jackson JG, Krizman EN, et al. Genetic deletion of the neuronal glutamate transporter, EAAC1, results in decreased neuronal death after pilocarpine-induced status epilepticus[J]. Neurochem Int,2013,online, doi:dx.doi.org/10.1016/j.neuint.2013.11.013
[184]Smeland OB, Hadera MG, McDonald TS, et al. Brain mitochondrial metabolic dysfunction and glutamate level reduction in the pilocarpine model of temporal lobe epilepsy in mice[J]. Journal of Cerebral Blood Flow & Metabolism,2013,33:1090-1097.
[185]Sepkuty JP, Cohen AS, Eccles C, et al. A neuronal glutamate transporter contributes to neurotransmitter GABA synthesis and epilepsy[J]. J Neurosci,2002,22(15):6372-6379.
[186]Kwan P, Schachter SC, Brodie MJ. Drug-resistant epilepsy[J]. N Engl J Med,2011,365: 919-926.
[187]Postschka H. Role of CNS efflux drug transporters in antiepileptic drug delivery: overcoming CNS efflux drug transport[J]. Adv Drug Deliv Rev,2012,64(10):943-952.
[188]Marchi N, Gonzalez-Martinez J, Nguyen MT, et al. Transporters in drug-refractory epilepsy:clinical significance [J]. Clinical Pharmacology & Therapeutics,2010,87 (1): 13-15.
[189]Lazarowski A, Czornyj L, Lubienieki F, et al. ABC transporters during epilepsy and mechanisms underlying multidrug resistance in refractory epilepsy [J]. Epilepsia,2007, 48(s5):140-149.
[190]Balan S, Iekshmi S, Radha K, et al. Major vault protein (MVP) gene polymorphisms and drug resistance in mesial temporal lobe epilepsy with hippocampal sclerosis [J]. Gene, 2013,526(2):449-453.
[191]Sillanpaa M, Schmidt D. Natural history of treated childhood-onset epilepsy: prospective, long-term population-based study[J].Brain,2006,129(3):617-624.
[192]Jackson GD. Epilepsy:hippocampal sclerosis-are we speaking the same language?[J]. Nature Review Neurology,2013,9:548-549.
[193]van Breemen MS, Wilms EB, Vecht CJ. Epilepsy in patients with brain tumours: epidemiology, mechanisms, and management[J]. Lancet Neurol,2007,6:421-430.
[194]Picot MC, Baldy-Moulinier M, Daures JP, et al. The prevalence of epilepsy and pharmacoresistant epilepsy in adults:a population-based study in a Western European country[J].Epilepsia,2008,49:1230-1238.
[195]Marchi N, Betto G, Fazio Q, et al. Blood-brain barrier damage and ain penetration of antiepileptic drugs:role of serum proteins and brain edema[J]. Epilepsia,2009,50:664-677.
[196]Chen YH, Wang CC, Xiao X, et al. Multidrug resistance-associated protein 1 decreases the concentrations of antiepileptic drugs in cortical extracellular fluid in amygdale kindling rats[J]. Acta Pharmacol Sin,2013,34(4)-473-479.
[197]Arican N, Kaya M, Kalayci R, et al. Effects of lipopolysaccharide on blood-brain barrier permeability during pentylenetetrazol-induced epileptic seizures in rats[J]. Life Sci,2006, 79:1-7.
[198]Marchi N, Angelov L, Masaryk T, et al. Seizure-promoting effect of blood-brain barrier disruption[J].Epilepsia,2007,48:732-742.
[199]Kaya M, Gurses C, Kalayci R, et al. Morphological and functional changes of blood-brain barrier in kindled rats with cortical dysplasia[J].Brain Res,2008,1208:181-191.
[200]Ahishali B, Kaya M, Orhan N, et al. Effects of levetiracetam on blood-brain barrier disturbances following hyperthermia-induced seizures in rats with cortical dysplasia[J]. Life Sci,2010,87:609-619.
[201]Rigau V, Morin M, Rousset MC, et al. Angiogenesis is associated with blood-brain barrier permeability in temporal lobe epilepsy[J].Brain,2007,130:1942-1956.
[202]Morin-Brureau M, Lebrun A, Rousset MC, et al. Epileptiform activity induces vascular remodeling and Zonula occludens 1 down-regulation in organotypic hippocampal cultures:role of VEGF signaling pathways[J]. J Neurosci,2011,31:10677-10688.
[203]Lamas M, Gonzalez-Mariscal L, Gutierrez R. Presence of claudins mRNA in the brain: selective modulation of expression by kindling epilepsy[J]. Brain Res Mol Brain Res, 2002,104:250-254.
[1]Schayer RW, Reilly MA. In vivo formation and catabolism of 14C-histamine in mouse brain[J]. Journal of Neurochemistry,1970,17(12):1649-1655.
[2]Pardridge WM. Brain drug targeting:the future of brain drug development[J]. Cambridge, UK:Cambridge University Press,2001.
[3]Pardridge WM. The blood-brain barrier:bottleneck in brain drug developmen[J]. NeuroRx,2005,2:3-14.
[4]Chen Y, Liu LH. Modern methods for delivery of drugs across the blood-brain barrier[J]. Adv Drug Deliv Rev,2012,64:640-665.
[5]Banks WA. Drug transport into the central nervous system:using newer findings about the blood-brain barriers[J]. Drug Deliv and Transl Res,2012,2:152-159.
[6]Alyautdin R, Khalin I, Nafeeza MI, et al. Nanoscale drug delivery systems and the blood-brain barrier[J]. International Journal of Nanomedicine,2014,9:795-811.
[7]Pardridge WM. Drug transport across the blood-brain barrier[J]. Journal of Cerebral Blood Flow & Metabolism,2012,32:1959-1972.
[8]Baum L, Kwan P. Antiepileptic drug delivery[J]. Adv Drug Deliv Rev,2012,64:885-886.
[9]Matsson P, Pedersen JM, Norinder U, et al. Identification of novel specific and general inhibitors of the three major human ATP-binding cassette transporters P-gp, BCRP, and MRP2 among registered drugs[J]. Pharmaceutical Research,2009,26(8):1816-1831.
[10]Ben-Menachem E. Medical management of refractory epilepsy-Practical treatment with novel antiepileptic drugs[J]. Epilepsia,2014,55(sl):3-8.
[11]Perucca P, Gilliam FG. Adverse effects of antiepileptic drugs[J]. The Lancet Neurology, 2012,11(9):792-802.
[12]Kinderen RJA, Evers SMAA, Rinkens R, et al. Side-effects of antiepileptic drugs:the economic burden[J]. Seizure:European Journal of Epilepsy,2014,23(3):184-190.
[13]Kr PS, Jangra MK, Yadav AK. Herbal and synthetic approaches for the treatment of epilepsy[J]. Int J Nutr Pharmacol Neurol Dis,2014,4:43-52.
[14]Pearl PL, Drillings IM, Conry JA. Herbs in epilepsy:evidence for efficacy, toxicity, and interactions [J]. Seminars in Pediatric Neurology,2011,18(3):203-208.
[15]Yu CP, Tsai SY, Kao LJ, et al. A Chinese herb formula decreases the monocarboxylate transporter-mediated absorption of valproic acid rats[J]. Phytomedicine,2013,20(7):648-653.
[16]Fong SYK, Gao Q, Zuo Z. Interaction of carbamazepine with herbs, dietary supplements, and foods:a systematic review[J]. Evidence-Based Complementary and Alternative Medicine,2013,2013:898261.
[17]Samuels N, Finkelstein Y, Singer SR, et al. Herbal medicine and epilepsy:proconvulsive effects and interactions with antiepileptic drugs[J]. Epilepsia,2008,49(3):373-380.
[18]逄冰,刘文科,周强,等.芳香药物效用探析[J].中医杂志,2013,54(18)：1616-1618.
[19]何俊余.引经药为何能引经报使[J].世界中医药,2011,6(6)：521.
[20]吴雪,欧阳丽娜,向大位,等.冰片及石菖蒲促进羟基红花黄色素A透过血脑屏障的实验研究[J].中草药,2011,42(4)：734-737.
[21]唐勇,漆伟,叶承莉,等.补阳还五汤加麝香辅助治疗脊髓损伤临床研究[J].中医学报,2013,28(2)：288-290.
[22]喻斌,阮鸣,董小平,等.不同时隔时间冰片处理对大鼠栀子苷脑靶效应的影响[J].中国药理学通报,2012,28(6)：862-866.
[23]冯宏业,葛朝丽.冰片对癫痫患者血清及脑脊液卡马西平药物浓度的作用[J].海南医学,2005,16(6)：11-12.
[24]吴珊,王凌.石菖蒲促进卡马西平透过血脑屏障的实验研究[J].福建医药杂志,2013,35(5)：67-84.
[25]陈瑞玲,赵志刚,张星虎,等.冰片对丙戊酸钠透过血脑屏障的影响[J].中国康复理论与实践,2007,13(2)：151-153.
[26]倪彩霞,曾南,汤奇.芳香开窍药对正常小鼠血脑屏障通透性的影响[J].江苏中医药,2011,43(2)：88-89.
[27]魏宇宁,刘萍,何新荣,等.微透析法研究冰片对头孢曲松在大鼠脑纹状体中含量的影响[J].中国中药杂志,2010,35(19)：2605-2608.
[28]王丹丹,王建,彭颖,等.四味芳香开窍药的挥发性成分对缺血缺氧PC12细胞及细胞内Ca2+的影响[J].西安交通大学学报(医学版),2012,33(3)：370-373.
[29]倪彩霞,曾南,许福会,等.芳香开窍药对脑缺血再灌注损伤大鼠血脑屏障影响的实验研究[J].中国中药杂志,2011,36(18)：2562-2566.
[30]杨洋,王世祥,房敏峰,等.安息香醛、香草醛和β-细辛醚对P-糖蛋白功能的影响[J].中成药,2012,34(7)：1364-1366.
[31]朱国栋.冰片开放血脑屏障及通过P糖蛋白介导的机制研究[D].广州：广州医学院,2009：32.
[32]王虹.石菖蒲活性成分醒脑开窍、透过血脑屏障作用机制研究[D].北京：中国人民解放军军医进修学院,2007：49.
[33]周金雯.天然冰片、合成冰片及薄荷脑对P-糖蛋白的影响及其机制研究[D].南京：南京师范大学,2011：48.
[34]占宏伟,刘洪彪,叶小娟,等.冰片对P-糖蛋白影响的99mTc-MIBI显像研究[J].中国现代药物应用,2012,6(22)：1-3.
[35]段美美,曾武,陈浩,等.天然冰片对顺铂在C6脑胶质瘤模型大鼠体内的药动学及 脑组织分布的影响[J].中药药理与临床,2013,29(5)：24-27.
[36]陈振振,杜守颖,陆洋,等.艾片与麝香酮芳香开窍作用机制研究[J].中药材2014,37(3)：462-466.
[37]洪艳丽,蒋凤荣.麝香酮对氧化应激损伤人血管内皮细胞凋亡的影响[J].中华中医药杂志,2011,26(9)：2178-2180.
[38]陈艳明,王宁生.冰片对血脑屏障体外模型细胞紧密连接和细胞吞饮囊泡的影响[J].中国中西医结合杂志,2004,24(7)：632-634.
[39]刘煜德,孙丹邈,黄小洵,等.冰片对BMSCs透过血脑屏障的影响[J].亚太传统医药,2007,3(7)：46-48.
[40]刘亚敏,赵光峰,夏鑫华,等.麝香配伍冰片对缺血再灌注损伤后血脑屏障的影响[J].北京中医药,2009,28(6)：459-462.
[41]梁雪冰,吴杰,赵国平,等.运用HPLC和GC-MS研究开心散有效抗抑郁成分大鼠吸收情况[J].辽宁中医杂志,2013,40(2)：365-367.
[42]陈怡君,周文斌,赵宝全,等.麝香酮对斑马鱼血脑屏障及其组成蛋白claudin5a的影响//第九届全国天然有机化学学术会议论文集[C].海南海口：[出版社不详],2012：132.
[43]葛朝丽,韩漫夫,白润涛,等.冰片促进血脑屏障开放的超微结构研究[J].中西医结合心脑血管病杂志,2008,6(10)：1183-1185.
[44]胡园,袁默,刘屏,等.石菖蒲对血脑屏障超微结构及通透性的影响[J].中国中药杂志,2009,34(3)：349-351.
[45]李荣伟,姚丽梅,宓穗卿,等.冰片对大鼠下丘脑组胺、5-羟色胺含量的影响[J].中药材,2004,27(12)：937-939.
[46]李伟荣,姚丽梅,宓穗卿,等.冰片开放血脑屏障作用与组胺和5-羟色胺的关系[J].中国临床康复,2006,10(3)：167-169.
[47]谢婷婷,王虹,刘屏,等.中药石菖蒲对脑内单胺类神经递质5-羟色胺水平的影响[J].中国药物应用与监测,2007,(3)：15-17.
[48]陈长才,柯以铨,徐如祥.5-羟色胺在脑微血管中的变化与血脑屏障的关系[J].中华医学杂志,1997,77(4)：298-299.
[49]李涛.汪受传治疗小儿癫痫经验[J].中医杂志,2013,54(17)：1458-1460.
[50]何迎春.朱良春治痰经验浅析[J].中医杂志,2012,53(21)：1812-1813.
[51]刘绪银.化痰熄风、化瘀通窍治疗癫痫—国医大师张学文治疗脑病经验之五[J].中医临床研究,2011,3(19)：23.
[52]田洪亮,朱万青,黄伟,等.王雪峰教授豁痰健脾论治小儿癫痫[J].中国中西医结合儿科学,2012,4(6)：485-486.
[53]司富春,宋雪杰,李洁,等.癫痫证候和方药分布规律文献分析[J].中医杂志,2014,55(6)： 508-512.
[54]王越,刘金民,李淑芳,等.癫痫中医证型及证候要素分布规律的文献研究[J].环球中医药,2013,6(1)：16-19.
[55]黄小波,张国君,陈文强,等.难治性癫痫中医证候聚类分析[J].中国中医药信息杂志,2011,18(12)：24-26.
[56]黄小波,张国君,王晓飞,等.难治性癫痫中医证候的判别分析[J].中华中医药杂志,2012,27(12)：3072-3076.
[57]李振光,王净净.从“痰瘀同治”论治难治性癫痫[J].中医学报,2013,28(181)：832-834.
[58]李伟,胡凯文,苏伟,等.浙贝母散剂逆转急性白血病多药耐药的临床研究[J].北京中医药大学学报,2004,27(1)：63-65.
[59]李泽慧,安超,胡凯文,等.浙贝母总碱对人肺腺癌A549/顺铂细胞耐药性的逆转作用[J].中国药理学与毒理学杂志,2013,27(3)：315-320.
[60]王耘,胡凯文,安超.贝母素乙联合氨苄西林舒巴坦抗耐药菌感染的体内实验研究[J].中华中医药杂志,2010,25(12)：2010-2013.
[61]顾政一,张裴,聂勇战,等.5种生物碱胃癌多药耐药逆转剂的筛选及机制研究[J].中草药,2012,43(6)：1151-1156.
[62]招丽君,廖正根,梁新丽,等Caco-2细胞单层模型研究葛根提取物中葛根素转运机制及白芷提取物对其转运的影响[J].中国药学杂志,2012,47(20)：1638-1642.
[63]梁新丽,招丽君,廖正根,等Caco-2细胞模型研究白芷提取物对P-糖蛋白功能的影响[J].中国医院药学杂志,2012,32(22)：1781-1785.
[64]祝婧云,梁新丽,王光发,等.白芷提取物对黄芩活性成分黄芩苷的吸收促进作用[J].药学学报,2011,46(2)：232-237.
[65]王姝麟,李霞,王小宁,等.欧白芷素对K562/A02细胞阿霉素耐药的逆转作用[J].中国天然药物,2011,9(2)：146-150.
[66]姜登钊.中药百部归经的研究及其在海洋中药研发中的应用[J].青岛：中国海洋大学,2010：73.
[67]周震,宋宛珊,王占奎,等.化痰通络法对急性脑梗死大鼠溶栓后血脑屏障通透性及海马内皮细胞超微结构的影响[J].中华行为医学与脑科学杂志,2012,21(6)：508-511.
[68]张玉莲,周震,宋宛珊,等.化痰通络方对急性脑梗死大鼠溶栓后血脑屏障相关构成蛋白表达的影响[J].中医杂志,2013,54(24)：2128-2134.
[69]侯文.基于“痰瘀同治”的健脑益智胶囊对颅脑损伤大鼠脑组织微循环的影响[D].西安：陕西中医学院,2011：25.
[70]郜菲.益气活血化痰通络法对脑缺血小鼠海马组织MMP-9、TIMP-1表达的影响[D].石家庄：河北医科大学,2011：34.
[71]韩为.益气活血化痰法对脑缺血再灌注大鼠葡萄糖转蛋白、细胞间粘附分子-1表达的 影响[D].北京：北京中医药大学,2006：84.
[72]樊帆,丁晶,张倩倩,等.癫痫持续状态大鼠脑水肿及血脑屏障破坏的动态观察[J].中国临床神经科学,2013,21(5)：498-503.
[73]陈基焱,黄吉春,高然,等.癫痫大鼠血脑屏障超微结构改变及妥泰的保护作用[J].解剖学报,2008,39(4)：498-501.
[74]古艳婷,马永刚,王明正,等.半夏生物总碱对癫痫大鼠海马氨基酸含量和GABAA受体mRNA表达的影响[J].中国药学(英文版),2009,18：252-256.
[75]杨蓉,王明正,成银霞.半夏等6中中药超临界CO2乙醇萃取物对青霉素诱发大鼠痫性放电和海马区相关递质含量的比较研究[J].中国中医基础医学杂志2013,19(5)：507-510,554.
[76]杨蓉,王明正,成银霞.天南星超临界CO2乙醇萃取抗惊厥作用的实验研究[J].中西医结合心脑血管病杂志,2013,11(6)：736-738.
[77]孔美珠.癫痫发作期中医证素分布规律的研究[D].福州：福建中医药大学,2013：14.
[78]刘永旭.癫痫从肝风痰瘀论治—闫也教授临床经验总结[D].沈阳：辽宁中医药大学,2011：18.
[79]谢炜,史国军,李长征,等.柴胡疏肝汤对难治性癫痫大鼠脑电图及多药耐药蛋白P-糖蛋白表达的影响[J].中国实验方剂学杂志,2011,17(3)：128-131.
[80]谢炜,陈伟军,孟春想,等.柴胡皂苷a对难治性癫痫大鼠多药耐药蛋白P-糖蛋白表达的影响[J].中国实验方剂学杂志,2013,19(9)：229-232.
[81]杨李华.钩藤生物总碱对耐药惊厥大鼠脑内P-gp基因表达的影响[D].太原：山西医科大学,2007：22.
[82]王永辉.柴胡总皂苷对小鼠部分药物代谢酶及P-糖蛋白的影响[D].广州：广州中医药大学,2012：54.
[83]冯丽敏,张娴,赵瑞芝.醋柴胡小分子水溶性部位抑制HEK293-Pgp细胞中P糖蛋白的外排功能[J].中国药理学通报,2013,29(12)：1684-1688.
[84]李淑雯,胡志方.香附醋制前后对Caco-2细胞P-糖蛋白功能和表达的影响[J].中国实验方剂学杂志,2013,19(16)：217-219.
[85]陈彦,王晋艳,辛然,等.柴胡皂苷对芍药苷在Caco-2细胞模型中吸收转运的影响[J].中国中药杂志,2012,37(12)：1850-1854.
[86]王晓丹,曾苏.天麻素在Caco-2细胞及Bcap37\Bcap37/MDR1细胞模型中的转运和摄取[J].药学学报(英文版),2010,45(12)：1497-1502.
[87]王俏.天麻素和天麻苷元的体内外代谢和脑靶向性研究[D].杭州：浙江大学,2007：94-95.
[88]徐虹.当归提取物与P-糖蛋白相互作用的初步研究[D].长沙：中南大学,2010：42.
[89]谢炜,李长征,鲍勇,等.戊四氮慢性点燃大鼠海马谷氨酸、γ-氨基丁酸阳性细胞变 化及柴胡总皂甙的干预作用[J].南方医科大学学报,2006,26(8)：1132-1135.
[90]谢炜,于云红,赵云燕.柴胡疏肝汤对戊四氮慢性点燃大鼠不同脑区兴奋性的影响[J].中国中药杂志,2010,35(12)：1619-1622.
[91]陈小银,田礼义.天麻素对戊四氮致痫大鼠海马氨基酸递质的影响[J].天津中医药,2009,26(6)：476-478.
[92]姚小卫.红藻酸癫痫大鼠不同脑区的5-HT含量变化[J].湖北中医学院学报,2009,11(5)：21-22.
[93]吴浪龙,李祖荣.不同脑区突触体内单胺类递质水平与惊厥发作和症状严重程度的相关性研究[J].中国康复理论与实践,2011,17(6)：546-548.
[94]吕晓钗,黄华品,林碗挥,等.脑内5-羟色胺减少对致痫大鼠癫痫发作及学习记忆的影响[J].中国应用生理学杂志,2012,28(3)：210-213,+1.
[95]Merlet I, Ostrowsky K, Costes N, et al.5-HT1A receptor binding and intracerebral activity in temporal lobe epilepsy:an [18F] MPPF-PET study[J]. Brain,2004,127 (Pt4):900-913.
[96]Hasler G, Bonwetsch R, Giovacchini C, et al.5-HT1A receptor binding in temporal lobe epilepsy patients with and without major depression[J]. Biol Psychiatry,2007,62(11): 1258-1264.
[97]郭长江,李亚军.单胺类神经递质在大鼠癫痫发作心脏损伤中的作用[J].陕西医学杂志,2008,37(3)：289-291.
[98]李娜,林卫红,营原秀贤.颞叶癫痫患者的心血管功能变化及相关因素分析[J].中风与神经疾病杂志,2009,26(2)：205-207.
[99]陶琳,孙美珍,杨萍,等.5-HT1A受体对癫痫伴发抑郁的影响及神经保护作用[J].中西医结合心脑血管病杂志,2011,9(6)：723-726.
[100]李琼,孙美珍,杨萍.5-羟色胺1A受体激动剂8-OH-DPAT对癫痫合并抑郁大鼠的干预作用及其机制研究[J].临床神经病学杂志,2013,26(3)：206-209.
[101]郑慧杰,舒友生,王开颜.5-羟色胺能对嗅海马联合皮层癫痫样放电的影响//第五届CAAE国际癫痫论坛会议论文集[C].重庆：[出版社不详],2013.
[102]高国丽,车光升,姜源,等.人参、天麻等复方总提取物对血管性痴呆大鼠脑组织单胺递质含量的影响[J].中国临床康复,2006,10(19)：182-183,186.
[103]周本宏,李小军,冯琪,等.天麻醇提取物对小鼠的抗抑郁作用[J].中国医院药学杂志,2007,27(11)：1525-1528.
[104]戈宏.柴胡皂苷抗抑郁作用及其机制的研究[D].长春：吉林大学,2010.
[105]崔广智,金树梅.芍药苷对强迫游泳小鼠脑内单胺递质的影响[J].天津中医药大学学报,2012,31(2)：83-84.
[106]周中流,刘永辉.香附提取物的抗抑郁或性及其作用机制研究[J].中国实验方剂学杂志, 2012,18(7)：191-193.
[107]王永志,杜仪,韩玉,等.柴胡疏肝散对抑郁症大鼠海马神经递质含量的影响[J].北京中医药,2014,33(1)：50-53.
[108]白海侠.从痰瘀论治癫痫的机理探讨[J].中医药导报,2012,18(5)：96-98.
[109]黄世敬,王永炎.癫痫虚气留滞病机探讨[J].世界中西医结合杂志,2013,8(6)：541-543,551.
[110]蔡宇,余绍蕾,陈冰.中药活性成分逆转K562/ADM耐药性聚类模糊研究[J].中国药学杂志,2006,41(13)：971-973.
[111]渡边由香(日).大黄甘草汤及其组成生药对P-谈干白的抑制作用//日本药学会第125次年会论文摘要[J].国际中医药杂志,2006,28(1)：48.
[112]贺兼斌,廖慧中,张贻秋,等.人参皂苷Rg3对小鼠肺腺癌多药耐药的逆转作用[J].实用肿瘤杂志,2012,27(4)：373-377.
[113]徐晓军,石淑文,汤永民,等.人参皂苷Rh2抗白血病多药耐药细胞K562/VCR作用研究[J].中草药,2010,41(7)：1131-1135.
[114]周方,许红梅.大黄素对肝内胆汁淤积大鼠P-gp表达的影响[J].中国中药杂志,2010,35(7)：908-911.
[115]宋娟,刘晓磊,何娟,等.川芎嗪和人参皂苷Rgl对Caco-2细胞P-糖蛋白功能和表达的影响[J].中国药学杂志,2008,43(13)：987-991.
[116]萨础拉,吕航,姜艳艳,等.三皂苷在大鼠外翻肠囊中的吸收及与P-糖蛋白相互作用研究[J].北京中医药大学学报,2011,34(12)：836-842.
[117]张艳,王平,王进荣,等.在体单向肠灌流模型研究大黄素的大鼠肠吸收特性[J].中药新药与临床药理,2012,23(3)：286-290.
[118]杨力,王晓娟,李洁,等.三七总皂苷对脑缺血再灌注大鼠脑内P-gp表达的影响[J].中国临床解剖学杂志,2013,31(4)：94-96.
[119]谢桂.大黄对脑出血大鼠脑内occludin mRNA表达的影响[D].长沙：中南大学,2010：16.
[120]李玉芳,刘坤,杨智航,等.川芎嗪对大鼠脑缺血再灌注后occludin表达的影响[J].中国公共卫生,2013,29(11)：1635-1637.
[121]刘坤,姚阳.水蛭素对大鼠脑出血后血脑屏障通透性和紧密连接相关蛋白claudin-5表达的作用[J].沈阳医学院学报,2011,13(3)：137-139.
[122]李玉芳,刘坤,倪月秋,等.川芎嗪对大鼠脑缺血再灌注后血脑屏障的保护作用及Claudin-5表达的影响[J].中国医科大学学报,2013,42(6)：511-514.
[123]彭璠.大黄对脑出血大鼠闭锁小带蛋白-1作用的研究[D].长沙：中南大学,2010：19.
[124]刘曾旭,余庆,王向东,等.复方丹参对严重烫伤大鼠血脑屏障的保护作用[J].中国临床解剖学杂志,2011,29(5)：565-567.
[125]朱海燕,高永红,吴爱明,等.三七总皂苷对铝暴露脑微血管内皮细胞胞质紧密黏连蛋白1表达的影响[J].中国中医药信息杂志,2012,19(9)：36-39.
[126]朱海燕,高永红,马涛,等.三七总皂苷对铝暴露体外血脑屏障通透性的影响[J].中西医结合心脑血管病杂志,2011,9(11)：1359-1361.
[127]陆莹,罗亚非,范瑞娟.当归补血汤对大鼠局灶性脑缺血再灌注血-脑屏障和大脑皮质神经元的影响[J].神经解剖学杂志,2013,29(3)：301-305.
[128]唐宇平,蔡定芳,刘军,等.大黄改善急性脑出血大鼠血脑屏障损伤的水通道蛋白-4机理研究[J].中国中西医结合杂志,2006,26(2)：152-156.
[129]王晓红.丹参酮、血塞通对TNF-a诱导表达的影响及其机制研究[D].北京：北京中医药大学,2013：54.
[130]李建生,刘敬霞,孙捷,等.大黄苷元对骨髓间充质干细胞移植脑缺血大鼠血脑屏障的作用与机制[J].中国药理学通报,2008,24(12)：1628-1633.
[131]李建生,刘敬霞,孙捷,等.大黄苷元对骨髓间充质干细胞移植脑缺血大鼠基质金属蛋白酶的影响[J].中西医结合学报,2008,6(8)：810-816.
[132]李长栋,荔志云,白海,等.大黄素甲醚联合脐带间充质干细胞移植对创伤性脑损伤大鼠MMP-9和TIMP-1蛋白酶的影响[J].创伤外科杂志,2013,15(4)：306-309.
[133]李浩,张多斌,吴岚,等.丹参酮ⅡA对脑缺血再灌注损伤大鼠磷酸化p38MAPK和MMP-9表达及细胞凋亡的影响[J].中风与神经疾病杂志,2013,30(3)：229-233.
[134]唐超.丹参酮ⅡA对小鼠脑血管内皮细胞内皮素系统的影响[D].沈阳：中国医科大学,2008：3-4.
[135]同病异治对戊四氮点燃大鼠海马区谷氨酸代谢通路的影响[J].中国中西医结合杂志,2013,33(1)：95-99.
[1]李世绰,郑晓瑛,吴立文.中国癫痫预防与控制绿皮书[M].北京：北京大学出版社,2009：2.
[2]孟红梅,李娜,崔俐,等.吉林省部分农村地区癫痫流行病学调查[J].中风与神经疾病杂志,2010,27(12)：1108.
[3]Kwan P, Arzimanoglou A, Berg AT, et al. Definition of drug resistant epilepsy. Consensus proposal by the ad hoc Task Force of the ILAE Commission on Therapeutic Strategies [J]. Epilepsia,2010,51(6):1069-1077.
[4]Kwan P, Schachter SC, Brodie MJ. Drug-Resistant Epilepsy[J]. N Engl J Med,2011,365: 919-926.
[5]Feldmann M, Asselin MC, Liu J, et al. P-glycoprotein expression and function in patients with temporal lobe epilepsy:a case-control study[J]. The Lancet Neurology,2013, 12(8):777-785.
[6]郑香春,李淑芳,刘金民.柴贝止痫汤单药及合并用药治疗难治性癫痫临床观察[J].天津中医药,2012,29(3)：224-226.
[7]李卫红,青雪梅,华茜,等.大鼠脑微血管内皮细胞条件培养液对皮层神经元活性的影响以及通络救脑注射液的干预作用[J].中华中医药杂志,2006,21(6)：334-337.
[8]Helms HC, Madelung R, Waagepetersen HS, et al. In vitro evidence for the brain glutamate efflux hypothesis:brain endothelial cells cocultured with astrocytes display a polarized brain-blood transport of glutamate [J]. GLIA,2012,60:882-893.
[9]Bernas MJ, Cardoso FL, Daley SK, et al. Establishment of primary cultures of human brain microvascular endothelial cells:a new and simplified menthod to obtain cells for an in vitro model of the blood-brain barrier[J]. Nat Protoc,2010,5(7):1262-1272.
[10]Li GL, Simon MJ, Cancel LM, et al. Permeability of endothelial and astrocyte cocultures: in vitro blood-brain barrier models for drug delivery studies[J]. Annals of Biomedical Engineering,2010,38(8):2499-2511.
[11]Wolburg H, Noell S, Mack A, et al. Brain endothelial cells and the glio-vascular complex[J]. Cell Tissue Res,2009,335:75-96.
[12]Ge S, Pachter JS. Isolation and culture of microvascular endothelial cells from murine spinal cord[J]. JNeuroimmunol,2006,177:209-214.
[13]Hatherell K, Couraud PO, Romero IA, et al. Development of a three-dimensional, all-human in vitro model of the blood-brain barrier using mono-, co-, and tri-cultivation transwell models[J]. Journal of Neurosicence Methods,2011,199(2):223-229.
[14]Kuo YC, Lu CH. Effect of human astrocytes on the characterisstics of human brain-microvascular endothelial cells in the blood-brian barrier[J]. Colloids and Surfaces B:Biointerfaces,2011,86(1):225-231.
[15]Thanabalasundaram G, Schneidewind J, Pieper C, et al. The impact of pericytes on the blood-brian barrier integrity depends critically on the pericyte differentitation stage[J].The International Journal of Biochemistry & Cell Biology,2011,43(9):1284-1293.
[16]Thanabalasundaram G, Pieper C, Lischper M, et al. Regulation of the blood-brain integrity by pericytes via matrix metalloproteinases mediated activation of vascular endothelial growth factor in vitro[J]. Brain Research,2010,1347:1-10.
[17]Haseloff RF, Blasig IE, Bauer HC, et al. In search of the astrocytic factor(s) modulating blood-brain barrier functions in brain capillary endothelial cells in vitro[J]. Cellular and Molecular Neurobiology,2005,25(1):25-39.
[18]王喜军.中药血清药物化学的研究动态及发展趋势[J].中国中药杂志,2006,31(10)：789-791.
[19]王洪武,倪青,林兰.中药含药血清的研究进展及其在中医学中的应用[J].北京中医药,2008,27(9)：698-701.
[20]王国佐.血清药理学方法在中药研究中的进展[J].湖南中医药大学学报,2007,27(3)：78-80.
[21]贺石林,葛金文,贺蓉,等.质疑血清药理学,加强多层次半体内实验研究[J].中国药理学通报,2005,21(3)：277-279.
[22]葛金文,朱慧斌,王宇红,等.关于中药血清药理学方法的杂思考[J].世界科学技术—中医药现代化,2008,10(6)：16-22.
[23]韩笑,刘建勋,林成仁.血清药理学关键问题的存疑与讨论[J].中药药理与临床,2009,25(2)：122-124.
[24]陈赐慧,花宝金.关于中药血清药理学实验的几个问题和探讨[J].中华中医药学刊,2013,31(1)：46-48.
[25]林圆圆,杜武勋,张少强,等.基于血清药理学的中药复方时效关系研究[J].中医杂志,2013,54(14)：1175-1178.
[26]Loscher W, Luna C, Romermann K, et al. Do ATP-binding cassette transporters cause pharmacoresistance in epilepsy? Problems and approaches in determining which anti-epileptic drugs are affected[J]. Curr.Pharm.Des,2011,17:2808-2828.
[27]Zhang C, Kwan P, Zuo Z, et al. The transport of antiepileptic drugs by P-glycoprotein[J]. Adv.Drug Delivery Rev,2012,64:930-942.
[28]Loscher W. Role of drug efflux transporters in the brain for drug disposition and treatment of brain diseases[J]. Prog Neurobiol,2005,76:22-76.
[29]Luna-Tortos C, Fedrowitz M, Loscher W. Several major antiepileptic drugs are substrates for human P-glycoprotein[J]. Neuropharmacology,2008,55(8):1364-1375.
[30]Bauer B, Hartz A.M.S, Pekcec A, et al. Seizure-induced up-regulation of P-glycoprotein at the blood-brain barrier through glutamate and cyclooxygenase-2 signaling[J]. Mol Pharmacol,2008,73:1444-1453.
[31]刘金民,江涛.中医癫痫病证诊治标准化的思考[J].中西医结合学报,2006,4(6)：572-574.
[32]李淑芳.颞叶癫痫中医证候研究及柴贝止痫汤对癫痫大鼠GABAARal、 NMDAR1表达的影响[D].北京：北京中医药大学,2009.
[33]谢炜,陈伟军,孟春想,等.柴胡皂苷a对难治性癫痫大鼠多药耐药蛋白P-糖蛋白表达的影响[J].中国实验方剂学杂志,2013,19(9)：229-232.
[34]王俏,陈国神.天麻苷元大鼠鼻腔和静脉注射给药的脑药动学研究[J].中国新药杂志,2010,19(8)：708-712.
[35]胡园,袁默,刘屏,等.石菖蒲对血脑屏障超微结构及通透性的影响[J].中国中药杂志,2009,34(3)：349-351.
[36]李泽慧,安超,胡凯文,等.浙贝母总生物碱对人肺腺癌A549/顺铂细胞耐药性的逆转作用[J].中国药理学与毒理学杂志,2013,27(3)：315-320.
[37]杨洋,王世祥,房敏峰,等.安息香醛、香草醛和p-细辛醚对P-糖蛋白功能的影响[J].中成药,2012,34(7)：1364-1366.
[38]彭向前,冯玮,张文会.半夏醇提取液逆转多药耐药细胞系K562/A02的耐药性[J].中国实验方剂学杂志,2012,18(18)：157-160.
[1]Mao QC, Unadkat JD. Role of the breast cancer resistance protein(ABCG2) in drug transport[J]. The AAPS Journal,2005,7(1):E118-133.
[2]李卫红,青雪梅,华茜,等.大鼠脑微血管内皮细胞条件培养液对皮层神经元活性的影响以及通络救脑注射液的干预作用[J].中华中医药杂志,2006,21(6)：334-337.
[3]Narang VS, Fraga C, Kumar N, et al. Dexamethasone increases expression and activity of multidrug resistance transporters at the rat blood-brain barrier[J]. Am J Physiol Cell Physiol,2008,295:C440-C450.
[4]Sukowati CHC, Rosso N, Pascut D, et al. Gene and functional up-regulation of the BCRP/ABCG2 transporter in hepatocellular carcinoma[J].BMC Gastroenterology,2012, 12:160.
[5]Liu JYW, Thom M, Catarino CB, et al. Neuropathology of the blood-brain barrier and pharmaco-resistance in human epilepsy [J]. Brain,2012,135:3115-3133.
[6]Englund G, Jacobson A, Rorsman F, et al. Efflux transporters in ulcerative colitis: decreased expression of BCRP(ABCG2) and Pgp(ABCB1)[J]. Inflamm Bowel Dis,2007, 13:291-297.
[7]Nakanishi H, Yonezawa A, Matsubara K, et al. Impact of P-glycoprotein and breast cancer resistance protein on the brain distribution of antiepileptic drugs in knockout mouse models[J]. European Journal of Pharmacology,2013,710(1-3):20-28.
[8]Li G, Simon MJ, Cancel LM, et al. Permeability of endothelial and astrocyte cocultures: In vitro blood-brain barrier models for drug delivery studies[J]. Annals of Biomedical Engineering,2010,38(8):2499-2511.
[9]赵康峰,王种,孔建,等.不同血脑屏障模型的建立及其功能特点[J].环境与健康杂志,2012,29(2)：127-130.
[10]Wilhelm I, Fazakas C, Krizbai I A. In vitro models of the blood-brain barrier[J]. Acta Neurobiol Exp,2011,71:113-128.
[11]Kliewer SA, Goodwin B, Willson TM. The nuclear pregnane X receptor:a key regulator of xenobiotic metabolism[J]. Endocr Rev,2002,23:687-702.
[12]Bauer B, Hartz AMS, Fricker G, et al. Pregnane X receptor up-regulation of P-glycoptrotein expression and transport function at the blood-brain barrier[J]. Mol Pharmacol,2004,66(3):413-419.
[13]Swales KE, Moore R, Truss NJ, et al. Pregnane X receptor regulates drug metabolism and transport in the vasculature and protects from oxidative stress[J]. Cardiovasc Res, 2012,93(4):674-681.
[14]Zhang YH, Lu M, Sun XR, et al. Expression and activity of P-glycoprotein elevated by dexamethasone in culture retinal pigment epithelium involve glucocorticoid receptor and pregnane X receptor[J]. IOVS,2012,53(7):3508-3515.
[15]Malekshah OM, Lage H, Bahrami AR, et al. PXR and NF-κB correlate with the inducing effects of IL-1(3 and TNF-a on ABCG2 expression in breast cancer cell lines[J]. European Journal of Pharmaceutical Sciences,2012,47(2):474-480.
[16]Mosaffa F, Kalalinia F, Lage H, et al. Pro-inflammatory cytokines interleukin-1p, interleukin6 and tumor necrosis factor-a alter the expression of ABCG2 in cervix and gastric cancer cells[J]. Mol Cell Biochem,2012,363:385-393.
[17]Das A, Wallace IV GC, Holmes C, et al. Hippocampal tissue of patients with refractory temporal lobe epilepsy is associated with astrocyte activation, inflammation, and altered expression of channels and receptors[J]. Neuroscience,2012,220:237-246.
[18]Lzzo JG, Wu X, Wu TT, et al. Therapy-induced expression of NF-kappa B portends poor prognosis in patients with localized esophageal cancer undergoing preoperative chemo-radiation[J]. Dis Esophagus,2009,22(2):127-132.
[19]Lee SH, Kim H, Hwang JH, et al. Breast cancer resistance protein expression is associated with early recurrence and decreased survival in resectable pancreatic cancer patients[J]. Pathology International,2012,62(3):167-175.
[1]Loscher W. Animal Models of intractable Epilepsy [J].Progress in Neurobiology,1991, 53:239-258.
[2]Aronica E, Gorter J A, Redeker S, et al. Localization of breast cancer resistance protein (BCRP) in microvessel endothelium of human control and epileptic brain[J]. Epilepsia, 2005,46(6):849-857.
[3]Van Vliet E A, Redeker S, Aronica E, et al. Expression of multidrug transporters MRP1, MRP2, and BCRP shortly after status epilepticus, during the latent period, and in chronic epileptic rats[J]. Epilepsia,2005,46(10):1569-1580.
[4]Kedersha NL,Rome LH. Isolation and characterization of a novel ribonucle protein particle:large structures contain a single species of small RNA [J]. Cell Biol,1986,103(3): 699-709.
[5]Suprenant KA. Vault ribonucleoprotein particles:sarcophagi, gondolas, or safety deposit boxes?[J].Biochemistry,2002,41(49):14447-14454.
[6]Kickhoefer VA,Vasu SK, Rome LH. Vaults are the answer,what is the question? [J].Trends Cell Biol,1996,6(5):174-178.
[7]Van Zon A, Mossink MH, Scheper RJ, et al The vault complex [J]. Cell Mol Life Sci,2003, 60(9):1828-1837.
[8]Rybarova S, Batekova M,Hodoroval L, et al. Immunohistochemical detection of LRP protein in the normal human lung[J]. Bratisl Lek Listy,2001,102(2):66-72.
[9]Scheper RJ, Broxteman HJ, Scheffer GL,et al. Overexpression of a Mr 110,000 vesicular protein in non-P-glycoprotein-mediated multidrug resistance[J].Cancer Res,1993,53(7): 1475-1479.
[10]Izpuierdo MA, Scheffer GL, Flens MJ,et al. Broad distribution of the multidrug resistance-related vault lung resistance protein in normal tissues and tumors[J].Am J Pathol,1996,148(3):877-887.
[11]Scheffer GL, Wijngaard PLJ, Fkens MJ, et al. The drug resistance-related protein LRP is the human major vault protein [J]. Nature Med,1995,1(6):578-582.
[12]Izquierdo MA, Vanderzee AG, Vermorken JB, et al. Drug resistance-associated marker LRP for response to chemotherapy and prognoses in advanced ovarian carcinoma[J]. J Nat Cancer Inst,1995,87(16):1230-1237.
[13]Aronica E, Gorter JA, Van vliet EA, et al. Overexpression of the human major vault protein in gangliogliomas[J].Epilepsia,2003,44(9):1166-1175.
[14]Fosang AJ, Last K, Gardiner P, et al. Development of a cleavage-site-specific monoclonal antibody for detecting metalloproteinase-derived aggrecan fragments:detection of franments in human synovial fluids[J].Biochem J,1995,310(ptl):337-343.
[15]Van vliet EA, Aronica E, Redeker S, et al. Expression and cellular distribution of major vault protein:A putative marker for pharmacoresistance in a rat model for temporal lobe epilepsy [J].Epilepsia,2004,45(12):1506-1516.
[16]Sisodiya SM, Martinian L, Scheffer G L, et al. Major Vault Protein,a Marker of Drug Resistance, Is Upregulated in Refractory Epilepsy[J] Epilepsia,2003,44(11):1388-1396.
[17]赵凤玲,孙佳红,张宝兰,等.补肾益气活血中药对大鼠缺血再灌注脑组织血管内皮生长因子表达和血脑屏障通透性的影响[J].中国医药导报,2013,10(2)：20-25.
[18]李净,周慧生,何玲,等.益气活血法对气虚血瘀脑缺血再灌注损伤大鼠血脑屏障通透性及ICAM-1、MMP-9/-2的影响[J].中国中医基础医学杂志,2012,18(5)：510-512.
[1]Eid T, Thomas MJ, Spencer D, et al. Loss of glutamine synthetase in the human epilepogenic hippocampus:possible mechanism for raised extracellular glutamate in mesial temporal lobe epilepsy[J]. The Lancet,2004,363(9402):28-37.
[2]Sarac S, Afzal S, Broholm H, et al. Excitatory amino acid transporters EAAT-1 and EAAT-2 in temporal lobe and hippocampus in intractable temporal lobe epilepsy[J]. APMIS;2009,117(4):291-301.
[3]Rogawski MA. AMPA receptors as a molecular target in epilepsy therapy[J]. Acta Neurologica Scandinavica,2013,127(s 197):9-18.
[4]Clasadonte J, Dong J, Hines DJ, et al. Astrocyte control of synaptic NMDA receptors contributes to the progressive development of temporal lobe epilepsy[J]. PNAS,2013, 110(43):17540-17545.
[5]张英丰,汪小根,吴阳,等.微透析技术进行药动学研究的发展趋势及局限性探讨[J].中国实验方剂学,2011,17(15)：270-273.
[6]王杰琼,张惠云.微透析技术结合色-质联用检测细胞外液神经递质研究进展[J].医学综述,2011,17(7)：1052-1055.
[7]王晔.CQM对三叉神经痛模型大鼠镇痛效应及其对脑内兴奋性氨基酸递质的影响[D].北京：中国中医科学院,2013：30-32.
[8]李鹏,张美玉,王丹巧,等.青藤碱对SSNI模型大鼠镇痛效应及脑内兴奋性氨基酸递质的影响[J].中国药理学通报,2012,28(10)：1365-1369.
© 2004-2018 中国地质图书馆版权所有 京ICP备05064691号 京公网安备11010802017129号 地址：北京市海淀区学院路29号 邮编：100083 电话：办公室：(+86 10)66554848；文献借阅、咨询服务、科技查新：66554700 |