脂多糖诱发急性牙髓炎致敏的三叉神经节功能蛋白质组学研究
详细信息    本馆镜像全文|  推荐本文 |  |   获取CNKI官网全文
摘要
目前,口腔颌面部急慢性疼痛的机制不明,而神经系统致敏的问题正是神经科学领域研究的难点和热点。在疼痛研究中,各种牙髓损伤动物模型具有很多优点,而急性牙髓炎是较为理性的病理性疼痛动物模型,对于研究牙髓和口颌面疼痛的机制具有重要价值。
     目的:本研究结合临床实际,采用开髓封LPS的方法,建立大鼠急性牙髓炎的病理性疼痛动物模型;研究不同牙髓炎症阶段脑干中相关核团c-fos和GFAP的变化时程,探讨中枢致敏机制;进而应用蛋白质组学新技术,筛选与鉴定急性牙髓炎致敏时三叉神经节异常表达蛋白,寻找痛觉相关蛋白。
     材料与方法:雄性SD大鼠,设正常对照组和实验组。实验组动物左上第一磨牙开髓,封LPS,于6小时、12小时、24小时、48小时取牙齿、三叉神经节和脑干组织,用HE染色方法观察牙髓炎症的发展变化,用免疫组化、western-blot的方法分析脑干三叉神经脊束核尾侧亚核(Vc)、三叉神经脊束核极间亚核(ⅵ)、三叉神经孤束核(NTS)核团内c-fos和GFAP的变化时程,用蛋白质组学方法分析三叉神经节功能表达差异蛋白。
     结果:
     1.HE染色结果:随着LPS封药时间的延长,穿髓点下方的炎症范围逐渐扩展,程度加重。12-24小时出现典型的急性牙髓炎的病理学变化,穿髓点下方大量中性粒细胞浸润伴有局限性小脓肿形成,牙髓组织充血、水肿渗出明显,成牙本质细胞排列紊乱,部分牙髓变性坏死。48小时部分动物病变扩展至根尖周组织。
     2.脑干c-fos蛋白变化时程:在LPS致急性牙髓致敏后,与对照组相比,实验组Vc核c-fos阳性神经元表达数目明显增加,并呈时间依赖性,24小时达到最高;对侧Vc核及V_i核的c-fos表达数目少于实验侧,但变化趋势与实验侧相近;NTS的c-fos阳性神经元数目显著增加,6h最高,随时间逐渐降低,48小时仍高于对照组。
     3.急性牙髓炎脑干中星形胶质细胞GFAP的变化时程:在LPS致急性牙髓炎致敏后,Vc变化时程慢于c-fos阳性神经元,24 h至48h数量增多,此时星形胶质细胞胞体变大,突起增粗,染色加深,与c-fos阳性神经元分布区域相近。对侧Vc未见显著变化。而三叉神经节的卫星胶质细胞48小时才出现较弱的阳性表达。
     4.蛋白质组分析鉴定出48个差异点蛋白质斑点,其中21个表达量上调,27个下调,经质谱检测出10个点,分别为甲状腺素运载蛋白;内质网蛋白ERp29;低分子量神经丝蛋白;盘膜边缘蛋白;血清白蛋白前体;外周髓磷脂P0蛋白;组织蛋白酶B;丙酮酸脱氢酶E1;复制蛋白A和细胞骨架肌动蛋白。
     结论:
     1.开髓封LPS可以有效的造成急性牙髓炎动物模型,是较好的痛觉致敏模型;
     2.在急性牙髓炎致敏过程中,随着炎症的进展,脑干相关核团的神经元和胶质细胞先后被激活,相互作用,共同造成神经系统的致敏;
     3.在鉴定的10种蛋白质中,包括了细胞结构蛋白、分子伴侣蛋白、生物合成相关蛋白、以及在应激反应和能量代谢等重要生命活动中起关键作用的酶,细胞骨架破坏、能量代谢改变、信号转导异常等共同参与了LPS急性牙髓致敏的形成;
     4.内质网蛋白ER29、神经丝蛋白及髓磷脂P0蛋白可能成为评价牙髓急性痛敏时程、疼痛程度及预测预后的生物指标,为进一步深入研究急性牙髓炎性致敏的分子机制提供重要的线索,对研究三叉神经节功能及口颌面部疼痛的诊断和治疗具有参考价值。
At present,the mechanism of orofacial pain still remain unclear,the central sensitization is becoming one hot and difficult area of neuroscience research.In the pain research,many dental pulp injury models with different advantages have been employed,of which the acute pulpitis model is an ideal pathological pain model,which is of great value for the research of dental pulp and orofacial pain.
     Object:Based on the dinical characteristics of acute pulpitis,a rat acute pulpitis model was induced by Lipopolysaccaride(LPS),the expression of c-fos and GFAP in related nudeus of brain stem was observed to explore the mechanism of central sensitization,after that,the abnormally expressed proteins in the trigeminal ganglion were screened with a proteomics method to find pain-related proteins.
     Materials and methods:male rats were divided into experiment and control group.The access to dental pulp of the left upper first molar was prepared and LPS was placed into cavity,at 6h,12h,24h,48h after operation,the teeth were extracted,immunohistochemistry and western blot method were used to analyze the expression of c-fos and GFAP in brain stem,and proteomics method was carried out to detect the differential expression of function proteins in trigeminal ganglion.
     Results:
     1.HE staining:showed that with the increased stimulating duration of LPS,the range of inflammation extended gradually,and the inflammation became more severe.From 12 to 24h,the typical pathological change of acute pulpitis appeared,the pulp tissue became congested along with apparent exudate, great amounts of neutrophilic granulocyte infiltrated to the area below the perforation of pulp chamber,local abscess formed,necrosis appeared in partial dental pulp tissue,and odontoblast became malalinemented.After 48h, this pathological change extended to periapical tissue in partial animals.
     2.After central sensitization induced by LPS,the c-fos positive neuron number in Vc increased significantly compared with control group,which is also time-dependent and reach the peak at 24h after operation.Though the c-fos positive neuron number in contralateral side of Vc was lower than that in ipsilateral side,the development trend was similar with ipsilateral side.The number of c-fos positive neuron in NTs also increased significantly till 6h after operation,and then decreased gradually,but was sill higher than control group.
     3.The change of GFAP expression in Vc appeared later than c-fos,from 24 to 48h the number of positive neuron increased,the astrocyte became larger and the process became thicker,the staining also became stronger,the distribution of GFAP positive neuron was similar with c-fos.No apparent change was found in the contralateral side.The astrocyte in trigeminal ganglion only showed weak staining at 48h after operation.
     4.Total 48 protein spots were founded,among which 21 were upregulated,27 were downregulated.Ten proteins were identified as thyroxine binding globulin,ERp29,neurofilament protein,peripherin,serum albumin precursor, peripheral myelin P0 protein,Cathepsin B,pyruvate dehydrogenase E1, replication protein A and actin.
     Conclusion:
     1.Acute pulpititiscould be induced by LPS plcaed in exposed dental pulp in rat, which is a suitable model for hyperalgesia research;
     2.In this acute pulpitis,model,with the development the inflammation,neuron and astrocyte in related nucleus were activated in succession during the process of central sensitization,both the neuron and astrocyte acted reciprocally leading to central sensitization.
     3.Ten proteins identified in this research included structural protein,chaperone proteins,biosynthesis related protein,and some enzymeswhich play a key role in the stress and energy metabolism,based on this diversity,we conclude that the destruction of cytoskeleton,the change of energy metabolism and abnormal signal transduction all together take part in formation of central sensitization induced by acute pul pitis;
     4.ERp29,neurofilament protein and peripheral myelin P0 protein might be the biological indicators for the duration,degree and prognosis of acute pulpitis and the important dues for mechanism of orofacial pain,which might also provide the references for the diagnosis and treatment of orofacial pain.
引文
1.Niederberger E,Geisslinger G.Proteomics in neuropathic pain research.Anesthesiology,2008,108(2):314-23.
    2.Byers MR,Narhi MV.Dental injury models.experimental tools for understanding neuroinflammatory interactions and polymodal nociceptor functions.Crit Rev Oral Biol Med,1999,10(1):4-39.
    3.Maltos KL,Menezes GB,Caliari MV,st al.Vascular and cellular responses to pro-inflammatory stimuli in rat dental pulp.Arch Oral Biol,2004,49(6):443-50.
    4.林正梅,凌均启,凌征宇等.实验性牙髓炎疼痛动物模型的建立.广东牙病防治,1999,7(4):249-251.
    5.Hashimoto S,Maeda M,Yamakita J,et al.Effects of zinc oxide-eugenol on leucocyte number and lipoxygenase products in artificially inflamed rat dental pulp.Arch Oral Biol,1990,35(2):87-93.
    6.吴朝栋.内毒素.诱生的细胞因子及其作用研究进展.国外医学:免疫学分册,1995,18(1):11-14.
    7.侯本祥 史俊南.内毒素脂多糖刺激大鼠牙髓的组织病理学反应.牙体牙髓牙周病学杂志,1997,7(1):12-15.
    8.侯本祥.内毒素诱导单核-巨噬细胞产生细胞因子的作用机理.国外医学:口腔医学分册,1997:24(4):201-204.
    9.Wakisaka S,Sasaki Y,Ichikawa H,st al.Increase in c-fos-like immunoreactivity in the trigeminal nucleus complex after dental treatment.Proc Finn Dent Soc,1992,88 Suppl 1:551-5.
    10.Hahn CL,Liewehr FR.Relationships between caries bacteria,host responses,and clinical signs and symptoms of pulpitis.J Endod,2007,33(3):213-9.
    11.Chudler EH,Byers MR.Behavioural responses following tooth injury in rats.Arch Oral Biol,2005,50(3):333-40.
    12.Chattipakorn SC,Sigurdsson A,Light AR,et al.Trigeminal c-Fos expression and behavioral responses to pulpal inflammation in ferrets.Pain,2002,99(1-2):61-9.
    1 Marota JJ,Crosby G,Uhl GR.Selective effects of pentobarbital and halothane on c-fos and jun-B gene expreesion in rat brain.Anesthesiology,1992,77(2):365-71.
    2 Magdalena CM,Navarro VP,Park DM,et al.C-fos expression in rat brain nuclei following incisor tooth movement.J Dent Res,2004,83(1):50-4.
    3 Navarro VP,Rocha MJ,Branco LG.Reduced central c-fos expression and febrile response to repeated LPS injection into periodontal tissue of rats Brain Res,2007,1152:57-63.
    4 Wakisaka S,Sasaki Y,Ichikawa H,et al.Increase in c-fos-like immunoreactivity in the trigeminal nucleus complex after dental treatment.Proc Finn Dent Soc,1992,88 Suppl 1:551-5.
    5 Iwata K,Takahashi O,Tsuboi Y,et al.Fos protein induction in the medullary dorsal horn and first segment of the spinal cord by tooth-pulp stimulation in cats.Pain,1998,75(1):27-36.
    6 Chattipakorn SC,Light AR,Willcockson HH,et al.The effect of fentanyl on c-fos expression in the trigeminal brainstem complex produced by pulpal heet stimulation in the ferret.Pain,1999,82(2):207-15.
    7 Cherkas PS,Huang TY,Pannicke T,et al.The effects of axotomy on neurons and satellite glial cells in mouse teigeminal ganglion.Pain,2004,110(1-2):290-8.
    8 Chattipakorn SC,Sigurdsson A,Light AR,et al.Trigeminal c-Fos expression and behavioral responses to pulpal inflammation in ferrets Pain,2002,99(1-2):61-9.
    9 Zhou Q,Imbe H,Dubner R,et al.Persistent Fos protein expression after orofacial deep or cutaneous tissue inflammation in rats:implications for persistent orofacial pain.J Comp Neurol,1999,412(2):276-91.
    10 Saade NE,Abou Jaoude PG,Saadeh FA,st al.Fos-like immunoreactivity induced by intraplantar injection of endotoxin and its reduction by morphine.Brain Res,1997,769(1):57-65.
    11 Takemura M,Nagase Y,Yoshida A,et al.The central projections of the monkey tooth pulp afferent neurons Sornatosens Mot Res,1993,10(2):217-27.
    12 Marfurt CF,Turner DF.The central projections of tooth pulp afferent neurons in the rat as determined by the transganglionic transport of horseradish peroxidase.J Comp Neurol,1984,223(4):535-47.
    13 Byers MR,Chudler EH,ladarola MJ.Chronic tooth pulp inflammation causes transient and persistent expression of Fos in dynorphin-rich regions of rat bralnstem.Brain Res,2000,861(2):191-207.
    14 Worsley MA,Davies SL,Clayton NM,et al.The effect of inflammation on Fos expression in the ferret trigeminal nucleus.Eur J Oral Sci,2007,115(1):40-7.
    15 Allen GV,Barbrick B,Esser MJ.Trigeminal-parabrachial connections:possible pathway for nociception-induced cardiovascular reflex responses.Braln Res,1996,715(1-2):125-35.
    16 Hamba M.Stimulation-induced responses of thetrigeminal caudal neuronsin the brainstem preparation isolated from newborn rats.Brain Res,1998,785(1):66-74.
    1.Ajima H,Kawano Y,Takagi R,et al.The exact expression of glial fibrillary acidic protein(GFAP)in trigeminal ganglion and dental pulp.Arch Histol Cytol,2001,64(5):503-11.
    2.Byers MR,Maeda T,Brown AM,et al.GFAP immunoreactivity and transcription in trigeminal and dental tissues of rats and transgenic GFP/GFAP mice.Microsc Res Tech,2004,65(6):295-307.
    3.袁华 段丽 饶志仁.大鼠三叉神经尾侧亚核内星形胶质细胞对疼痛刺激的反应及与神经元的关系.解剖学报,2003,34(6):563-567.
    4.Guo W,Wang H,Watanabe M,et al.Glial-cytokine-neuronal interactions underlying the mechanisms of persistent pain.J Neurosci, 2007,27(22):6006-18.
    5.兰莉 高蓓 饶志仁.脂多糖对大鼠中脑和桥脑内Fos、GFAP、OX42表达的影响.解剖学报,2005,36(1):24-27.
    6.葛煦 饶志仁 等.LPS激发大鼠延髓内脏带星形胶质细胞GFAP和神经元FOS表达水平的变化.中国神经科学杂志,2001,17(3):214-218.
    7.Steward O,Torre ER,Tornasulo R,el al.Neuronal activity up-regulates astroglial gene expression.Proc Natl Acad Sci USA,1991,88(15):6819-23.
    8.Chudler EH,Anderson LC,Byers MR.Trigeminal ganglion neuronal activity and glial fibrillary acidic protein immunoreactivity after inferior alveolar nerve crush in the adult rat.Pain,1997,73(2):141-9.
    9.Scholz J,Woolf CJ.The neuropathic pain triad:neurons,immune cells and glia.Nat Neurosci,2007,10(11):1361-8.
    10.Anderson LC,von Bartheld CS,Byers MR.NGF depletion reduces ipsilateral and contralateral trigaminal satellite cell reactions after inferior alveolar nerve injury in adult rats.Exp Neurol,1998,150(2):312-20.
    11.Thalakoti S,Patil VV,Damodaram S,et al.Neuron-glia signaling in trigeminal ganglion:implications for migraine pathology.Headache,2007,47(7):1008-23;discussion 24-5.
    12.Dublin P,Hanani M.Satellite glial cells in sensory ganglia:their possible contribution to inflammatory pain.Brain Behav Immun,2007,21(5):592-8.
    1 Wilkins MR, Sanchez JC, Gooley AA, et al. Progress with proteome projects: why all proteins expressed by a genome should be identified and how to do it. [J] Biotechnol Genet Eng Rev,1996,13:19-50.
    
    2 Seipelt J, Liebig HD, Sommergruber W, et al. 2A proteinase of human rhinovirus cleaves cytokeratin 8 in infected HeLa cells. [J] J Biol Chem, 2000, 275(26):20084-9.
    
    3 Wright JT, Hart TC. The genome projects: implications for dental practice and education. [J] J Dent Educ, 2002, 66(5):659-71.
    
    4 Triantafilou K, Triantafilou M. A biochemical approach reveals cell-surface molecules utilised by Picornaviridae: Human Parechovirus 1 and Echovirus 1. [J] J Cell Biochem,2001, 80(3): 373-81.
    
    5 Patel V, Leethanakul C, Gutkind JS. New approaches to the understanding of the molecular basis of oral cancer. [J] Crit Rev Oral Biol Med, 2001,12(1): 55-63.
    
    6 Hubbard MJ. Functional proteomics: The goalposts are moving.[J]Proteomics, 2002, 2(9):1069-78.
    
    7 Shnyder SD, Hubbard MJ. ERp29 is a ubiquitous resident of the endoplasmic reticulum with a distinct role in secretory protein production. [J] J Histochem Cytochem, 2002,50(4):557-66.
    
    8 Hubbard MJ, Faught MJ, Carlisle BH, et al. ToothPrint, a proteomic database for dental tissues. [J] Proteomics, 2001, 1(1):132-5.
    
    9 KojimaT, Andersen E, Sanchez JC, et al. Human gingival crevicular fluid contains MRP8 (S100A8) and MRP14 (S100A9), two calcium-binding proteins of the S100 family. [J]J Dent Res,2000, 79(2): 740-7.
    
    10 Nelson KE, Fleischmann RD, DeBoy RT, et al. Complete genome sequence of the oral pathogenic Bacterium porphyromonas gingivalis strain W83.[J]J Bacteriol,2003,185(18):5591-601.
    11 Demmer J,Zhou C,Hubbard MJ.Molecular cloning of ERp29,a novel and widely expressed resident of the endoplasmic reticulum.[J]FEBS Lett,1997,402(2-3):145-50.
    12 Hubbard MJ,McHugh NJ,Carne DL.Isolation of ERp29,a novel endoplasmic reticulum protein,from rat enamel cells evidence for a unique role in secretory-protein synthesis.[J]Eur J Biochem,2000,267(7):1945-57.
    13 Liepinsh E,Baryshev M,Sharipo A,et al.Thioredoxin fold as homodimerization module in the putative chaperone ERp29:NMR structures of the domains and experimental model of the 51 kDa dimer.[J]Structure,2001,9(6):457-71.
    14 Sargsyan E,Baryshev M,Backlund M,et al.Genomic organization and promoter characterization of the gene encoding a putative endoplasmic reticulum chaperone,ERp29.[J]Gene,2002,285(1-2):127-39.
    15 Moiseeva N,Swenson SD,Markland FS Jr,et al.Purification,crystallization and preliminary X-ray analysis of the disintegrin contortrostatin from Agkistrodon contortrix contortrix snake venom.[J]Acta Crystallogr D Biol Crystallogr,2002,58(Pt 12):2122-4.
    16 Al-Chalabi A,Miller CC.Neurofilaments and neurological disease.[J]Bioessays,2003,25(4):346-55.
    17 Gama Sosa MA,Friedrich VL Jr,DeGasperi R,et al.Human midsized neurofilament subunit induces motor neuron disease in transgenic mice.[J]Exp Neurol,2003,184(1):408-19.
    18 蒲昭霞,赵聪敏,鲁利群.丰富环境对缺氧缺血性脑损伤大鼠海马突触超微结构及突触素表达的影响.[J]第三军医大学学报,2006,28(8): 816-818.
    19 于若谷,赵聪敏,王丽雁等.丰富环境刺激对缺氧缺血性脑损伤大鼠脑超微结构改变及神经丝蛋白表达的影响.[J]中国组织工程研究与临床康复,2007,11(13):2503-06.
    20 于若谷,赵聪敏,王丽雁等.丰富环境干预后HIBD大鼠脑超微结构改变.[J]第三军医大学学报,2006,28(8):819-820.
    21 Faden AI,Jacobs TP,Feuerstein G,et al.Dopamine partially mediates the cardiovascular effects of naloxone after spinal injury.[J]Brain Res,1981,213(2):415-21.
    22 McCord JM.Oxygen-derived free radicals in postischemic tissue injury.[J]N Engl J Med,1985,312(3):159-63.
    23 Fried K,Arvidsson J,Robertson B,et al.Combined retrograde tracing and enzyme/immunohistochemistry of trigeminal ganglion cell bodies innervating tooth pulps in the rat.[J]Neuroscience,1989,33(1):101-9.
    24 Szabolcs MJ,Visser J,Shelanski ML,et al.Peripherin:a novel marker for the immunohistochemical study of malformations of the enteric nervous system.[J]Pediatr Pathol Lab Med,1996,16(1):51-70.
    25 Filbin MT,Tennekoon GI.Myelin PO-protein,more than just a structural protein?[J]Bioessays,1992,14(8):541-7.
    26 Runker AE,Kobsar Ⅰ,Fink T,et al.Pathology of a mouse mutation in peripheral myelin protein PO is characteristic of a severe and early onset form of human Charcot-Marie-Tooth type 1B disorder.[J]J Cell Biol,2004,165(4):565-73.
    27 Shames Ⅰ,Fraser A,Colby J,et al.Phenotypic differences between peripheral myelin protein-22(PMP22)and myelin protein zero(PO)mutations associated with Charcot-Marie-Tooth-related diseases.[J]J Neuropathol Exp Neurol,2003,62(7):751-64.
    28 Owens GC, Boyd CJ. Expressing antisense PO RNA in Schwann cells perturbs myelination. [J] Development, 1991,112(2):639-49.
    
    29 Yazaki T, Miura M, Asou H, et al. Peripheral myelin PO protein mediates neurite outgrowth of cortical neurons in vitro and axonal regeneration in vivo. [J] Neurosci Lett, 1994, 176(1):13-6.
    
    30 Kursula P. Structural properties of proteins specific to the myelin sheath. [J] Amino Acids, 2008, 34(2):175-85.
    
    31 Fischer S, Weishaupt A, Troppmair J, et al. Increase of MCP-1 (CCL2) in myelin mutant Schwann cells is mediated by MEK-ERK signaling pathway. [J] Glia, 2008, 56(8):836-43.
    [1]Dublin P,Hanani M.Satellite glial cells in sensory ganglia:their possible contribution to inflammatory pain.Brain Behav Immun,2007,21(5):592-598
    [2]陈琰,刘洪臣.牙痛的外周及中枢神经传导通路[J].中华老年口腔医学杂志,2006,4(2):108-111
    [3]Julius D,Basbaum Al.Molecular mechanisms of nociception[J].Nature,2001,413:203-210
    [4]Pannese E,Procacci P,Ledda M et al.Age-related reduction of the satellite cell sheath around spinal ganglion neurons in the rabbit[J].J Neurocytol,1996,25(2):137-146
    [5]Pannese E.Perikaryal surface specializations of neurons in sensory ganglia[J].Int Rev Cytol.2002,220(3):1-34
    [6]Ledda M,DePalo S,Pannese E.Ratios between number of neuroglial cells and number and volume of nerve cells in the spinal ganglia of two spedes of reptiles and three species of mammals[J].Tissue Call,2004,36(1):55-62
    [7]Donato R.a single receptor for several ligands and different cellular responses:the case of certain S100 proteins[J].Curr Mol Med,2007,7(8):711-724
    [8]Hanani M,Huang TY,Cherkas PS et al.Glial cell plasticity in sensory ganglia induced by nerve damage[J].Neuroscience,2002,114(2):279-283
    [9]Hanani M.Satellite glial cells in sensory ganglia:from form to function[J].Brain Research Reviews,2005,48(3):457-476
    [10]Hu]P,McLachlan EM.Macrophage and lymphocyte invasion of dorsal root ganglia after peripheral nerve lesions in the rat[J].Neuroscience,2002,112(1):23-38
    [11]Miller KE,Richards BA,Kriebel RM.Glutamine-,glutamine synthetase-,glutamate dehydrogenase- and pyruvate carboxylaseimmunoreactivities in the rat dorsal root ganglion and peripheral nerve[J].Brain Res,2002,945(2):202-211
    [12]Weick M,Cherkas PS,Pannicke T et al.P2 receptors in satellite glial cells intrigeminal ganglia of mice[J].Neuroscience,2003,120(4):969-977
    [13]Kumamoto T,Fukuhara N.Experimental neuropathy induced by methyl mercury compounds:autoradiographic study of GABA uptake by dorsal root ganglia[J].Eur Neurol,1986,25(4):269-277
    [14]Stebbing MJ,McLachlan EM,Sah P.Are there functional P2X receptors on cell bodies in intact dorsal root ganglia of rats?[J].Neuroscience,1998,86(4):1235-1244
    [15]Aoki E,Semba R,Kashiwamata S.Localization of nitric oxide-related substances in the peripheral nervoustissues[J].Brain Res,1993,620(1):142-145
    [16]Thippeswamy T,Morris R.The roles of nitric oxide in dorsal root ganglion neurons[J].Ann N Y Acad Sci,2002,962(2):103-110
    [17]Khodorova A,Fareed MU,Gokin AP et al.Local injection of endothelin-1produces pain-like behavior and excitation of nociception in rats[J].J Neurosci,2002,22(17):7788-7796
    [18]England S,Heblich F,James IF et al.Bradykinin evokes a calcium-activated chloride current in non-neuronal satellite cells isolated from neonatal dorsal root ganglion[J].J Physiol,2001,530(3):395-403
    [19]Heblich F,England S,Docherty RJ.Indirect actions of bradykinin on neonatal rat dorsal root ganglion neurones:a role for non-neuronal cells as nociceptors[J].J Physiol,2001,536(1):111 - 121
    [20]Braun N,Robson SC,Hammer K et al.Assodation of the Ecto-ATPase NTPDase2 with glial cells of the peripheral nervous system[J].Glia,2004,45(2):124-132
    [21]Shinder V,Lippmann RG.Cohen S et al.Structural basis of sympathetic sensory coupling in rat and human dorsal root ganglia following peripheral nerve injury[J].J Neurocytol,1999,28(9):743-761
    [22]Anderson LC,Barthfeld CS,Byers MR.NGF depletion reduces ipsilateral trigeminal satellite cell reactions after inferior alveolar nerve injury in adult rats[J].Neurol,1998,150(2):312-320
    [23]Elson K,Simmons A,Speck P.Satellite cell proliferation in murine sensory ganglia in response to scarification of the skin[J].Glia,2004,45(1):105-109
    [24]Zhou XF,Deng YS,Chie E et al.Satellite-cell-derived nerve growth factor and neurotrophin-3 are involved in noradrenergic sprouting in the dorsal root ganglia following peripheral nerve injury in the rat[J].Eur J Neurosd,1999,11(5):1711-1722
    [25]Soares HD,Chen SC,Morgan GI.Differential and prolonged expression of Fos-lacZ and Jun-lacZ in neurons,glia,and muscle following sciatic nerve damage[J].Exp Neurol,2001,167(1):1 - 14
    1.Woolf CJ,Mannion RJ:Neuropathic pain:Aeliology,symptoms,mechanisms,and management.Lancet 1999;353:1959-64
    2.Sindrup SH,Jensen TS:Efficacy of pharmacological treatments of neuropathic pain:An update and effect related to mechanism of drug action.Pain 1999;83:389-400
    3.Hansson PT,Dickenson AH:Pharmacological treatment of peripheral neuropathic pain conditions based on shared commonalities despite multiple etiologies.Pain 2005;113:251-4
    4.Chen H,Lamer TJ,Rho RH,Marshall KA,Sitzman BT,Ghazi SM,Brewer RP.Contemporary management of neuropathic pain for the primary care physician.Mayo Clin Proc 2004;79:1533-45
    5.Kingery WS:A critical review of controlled clinical trials for peripheral neuropathic pain and complex regional pain syndromes.Pain 1997;73:123-39
    6.Koltzenburg M:Painful neuropathies.Curr Opin Neurol 1998;11:515-21
    7.Campbell JN,Meyer RA:Mechanisms of neuropathic pain.Neuron 2006;52:77-92
    8.Orth AP,Batalov S,Perrone M,Chanda SK:The promise of genomics to identify novel therapeutic targets.Expert Opin Ther Targets 2004;8:587-96
    9.O'Farrell PH:High resolution two-dimensional electrophoresis of proteins.J Biol Chem 1975;250:4007-21
    10.Matsumoto H,Komori N:Protein identification on two-dimensional gels archived nearly two decades ago by in-gel digestion and matrix-assisted laser desorption ionization time-of-flight mass spectrometry.Anal Biochem 1999;270:176-9
    11.Gorg A,Obermaier C,Boguth G,Harder A,Scheibe B,Wildgruber R,Weiss W:The current state of two-dimensional eiectrophoresis with immobilized pH gradients.Electrophoresis 2000;21:1037-53
    12.Rosenfeld J,Capdevielle J,Guillemot JC,Ferrara P.In-gel digestion of proteins for internal sequence analysis after one- or two-dimensional gel electrophoresis.Anal Biochem 1992;203:173-9
    13.Burre J,Beckhaus T,Corvey C,Karas M,Zimmermann H,Volknandt W:Synaptic vesicle proteins under conditions of rest and activation:Analysis by 2-D difference gel electrophoresis.Electrophoresis 2006;27:3488-96
    14.Banks RE,Dunn MJ,Hochstrasser DF,Sanchez JC,Blackstock W,Pappin DJ,Selby PJ:Proteomics:New perspectives,new biomedical opportunities.Lancet 2000;356:1749-56
    15.Engwegen JY,Gast MC,Schellens JH,Beijnen JH:Clinical proteomics:Searching for better tumour markers with SELDI-TOF mass spectrometry.Trends Pharmacol Sci 2006;27:251-9
    16.Brehmer D,Godl K,Zech B,Wissing J,Daub H:Proteome-wide identification of cellular targets affected by bisindolylmaleimide-type protein kinase Cinhibitors.Mol Cell Proteomics 2004;3:490-500
    17.Wang LX,Wang ZJ:Animal and cellular models of chronic pain.Adv Drug Deliv Rev 2003;55:949-65
    18.Kim KJ,Yoon YW,Chung JM:Comparison of three rodent neuropathic pain models.Exp Brain Res 1997;113:200-6
    19.Lee DH,Chung K,Chung JM:Strain differences in adrenergic sensitivity of neuropathic pain behaviors in an experimental rat model.Neuroreport 1997;8:3453-6
    20.Gordh T,Chu H,Sharma HS:Spinal nerve lesion alters blood-spinal cord barrier function and activates astrocytes in the rat.Pain 2006;124:211-21
    21.Perlson E,Hanz S,Ben-Yaakov K,Segal-Ruder Y,Seger R,Fainzilber M:Vimentin-dependent spatial translocation of an activated MAP kinase in injured nerve.Neuron 2005;45:715-26
    22.Sharma HS,Gordh T,Wiklund L,Mohanty S,Sjoquist PO:Spinal cord injury induced heat shock protein expression is reduced by an antioxidant compound H-290/51:An experimental study using light and electron microscopy in the rat.J Neural Transm 2006;113:521-36
    23.Yenari MA,Giffard RG,Sapolsky RM,Steinberg GK:The neuroprotective potential of heat shock protein 70(HSP70).Mol Med Today 1999;5:525-31
    24.Costigan M,Mannion RJ,Kendall G,Lewis SE,Campagna JA,Coggeshall RE,Meridith-Middleton J,Tate S,Woolf CJ:Heat shock protein 27:Developmental regulation and expression after peripheral nerve injury.J Neurosci 1998;18:5891-900
    25.Kretz A,Schmeer C,Tausch S,Isenmann S:Simvastatin promotes heat shock protein 27 expression and Akt activation in the rat retina and protects axotomized retinal ganglion cellsin vivo.Neurobiol Dis 2006;21:421-30
    26.Latchman DS:HSP27 and cell survival in neurones.Int J Hyperthermia 2005;21:393-402
    27.BoylesJK,Notterpek LM,Anderson LJ:Accumulation of apolipoproteins in the regenerating and remyelinating mammalian peripheral nerve:Identification of apolipoprotein D,apolipoprotein A-Ⅳ,apolipoprotein E,and apolipoprotein A-Ⅰ.J Biol Chem 1990;265:17805-15
    28.Ignatius MJ,Gebicke-Harter PJ,Skene JH,Schilling JW,Weisgraber KH,Mahley RW,Shooter EM:Expression of spolipoprotein E during nerve degeneration and regeneration.Proc Natl Acad Sci USA 1986;83:1125-9
    29.Granville DJ,Gottlieb RA:The mitochondrial voltage-dependent anion channel(VDAC)as a therapeutic target for initiating cell death.Curr Med Chem 2003;10:1527-33
    30.Pesheva P,Kuklinski S,Schmitz B,Probstmeier R:Galectin-3 promotes neural cell adhesi on and neurite growth.J Neurosci Res 1998;54:639-54
    31.Cameron AA,Dougherty PM,Garrison CJ,Willis WD,Carlton SM:The endogenous lectin RL-29 is transynaptically induced in dorsal horn neurons following peripheral neuropathy in the rat.Brain Res 1993;620:64-71

© 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