药物干预对帕金森病的治疗作用以及帕金森病的早期诊断
详细信息    本馆镜像全文|  推荐本文 |  |   获取CNKI官网全文
摘要
目的:帕金森病(Parkinson's disease,PD)是影响中老年人身体健康的主要神经退行性疾病,其病因尚不清楚。因此,目前尚没有针对病因的治疗措施。左旋多巴作为治疗PD的最有效的药物,只能缓解症状,并不能阻止或者减缓PD的进展,相反左旋多巴可能对多巴胺(dopamine,DA)能神经元有促凋亡和加速神经元变性坏死的作用。因此,加强PD的病因学研究、研究治疗PD的有效药物,对于提高人类健康水平具有重大意义。
     PD是一种慢性进行性变性疾病,起病隐匿,诊断主要依靠临床表现,没有特异性,符合率大约在75%~80%,并且在出现临床症状时,DA能神经元死亡已在80%以上。随着神经保护治疗策略的提出和神经营养因子的研究,越来越需要早期诊断PD,早期给予神经保护性治疗,对于改善PD患者的预后,提高其生活质量具有极其重要的意义。
     本课题用6-羟基多巴(6-OHDA)立体定向注射到大鼠纹状体部位制作PD模型,利用行为学、免疫组化和液体闪烁计数法,对免疫、凋亡与PD的发病机制之间的关系进行研究,以及对外周血淋巴细胞(Peripheral Blood Lymphocytes,PBL)中的多巴胺转运体(Dopamine Transporter,DAT)作为早期诊断PD的指标进行评价。
     方法:用6-OHDA两点注射右侧纹状体制作单侧PD大鼠模型,注射等剂量的生理盐水的假手术组为对照。实验共分为6组,每组6只:对照组、模型组、美多巴组、司来吉兰组、颤复宁中药组和雷公藤多甙组,对照组和模型组生理盐水灌胃,美多巴组、司来吉兰组、颤复宁中药组、雷公藤多甙组同时间等剂
Objective: Parkinson' s disease (PD) is the main neurodegenerative disorder that influences the middle age and old peoples, its cause is still not clear. Therefore, there isn' t treatment measure aiming at the cause of disease currently. As the most valid medicine, levodopa can alleviate symptom simply, and can' t obstruct and decelerate the progress of PD, contrarily levodopa can accelerate apoptosis and putrescence of dopamine neurons. Therefore, exploring the etiology and valid medicine can exaltate mankind' s health level significantly.
    PD is chronic and progressive neurodegenerative disease, which is diagnosed mainly depending on the clinic performance without particularity. Thus, the effective rate of diagnosis is about 75%-80%, and while clinical symptom appears, death of dopamine neurons have exceeded 80%. Moreover, put forward with the research of nerve nourishment factor along with the neuroprotective strategy, the patients of PD need more and more to be examined and given neuroprotective treatment in early days. It is important to improve the patient' s prognosis and the living quality.
    In this study, we injected 6-OHDA into the right striatum of rat to prepare the hemilateral model of PD. Behavior, immunohistochemical
引文
[1] Mena MA, Davila V, Sulzer D, et al. Neurotrophic effects of L-DOPA in postnatal midbrain dopamine neuron/cortical astrocyte cocultures. J Neurochem, 1997, 69 (4) : 1398-1408.
    [2] Zou L, Jankovic J, Rowe DB, et al. Neuroprotection by pramipexole against dopamine-and levodopa-induced cytotoxicity. Life Sci, 1999, 64 (15) : 1275-1285.
    [3] Mitchell P. Human xenotransplantation trials may be licensed in the UK. Lancet, 1998, 352 (9126) : 464.
    [4] Blunt SB, Jenner P, Marsden CD, et al. Suppressive effect of L-dopa on dopamine cells remaining in the ventral tegmental area of rats previously exposed to the neurotoxin 6-hydroxydopamine. Mov Disord, 1993, 8 (2) : 129-133.
    [5] Murer MG, Raisman-Vozari R, Gershanik O, et al. Levodopa in Parkinson's disease: neurotoxicity issue laid to rest? Drug Saf, 1999, 21 (5) : 339-352.
    [6] Dziewczapolski G, Murer G, Agid Y, et al. Absence of neurotoxicity of chronic L-DOPA in 6-hydroxydopamine-lesioned rats. Neuroreport, 1997, 8 (4) : 975-979.
    [7] Murer MG, Dziewczapolski G, Menalled LB, et al. Chronic levodopa is not toxic for remaining dopamine neurons, but instead promotes their recovery, in rats with moderate nigrostriatal lesions. Ann Neurol, 1998, 43 (5) : 561-575.
    [8] Deleu D, Northway MG, Hanssens Y, et al. Clinical pharmacokinetic and pharmacodynamic properties of drugs used in the treatment of Parkinson's disease. Clin Pharmacokinet, 2002, 41 (4) : 261-309.
    [9] 刘道宽,蒋雨平,江澄川,等主编.锥体外系疾病[M].上海科学技术出版社,2000:97.
    [10] Ebadi M, Sharma S, Shavali S, et al. Neuroprotective actions of selegiline. J Neurosci Res, 2002, 67 (3) : 285-289.
    [11] Myllyla VV, Sotaniemi KA, Yuorinen JA, et al. Selegiline as initial treatment in de novo parkinsonian patients. Neurology, 1992, 42 (2) : 339-343.
    [12] The Parkinson Study Group. Effects of tocopherol and deprenyl on the progression of disability in early Parkinson's disease. N Engl J Med, 1993, 328 (3) : 176-183.
    [13] 许继平,孙丰润.自拟中药颤复宁散治疗帕金森病的临床疗效研究.滨州医学院学报,1994,17(2):115-121.
    [14] 于长本,曲昌盛,侯强.颤复宁治疗帕金森病15例疗效观察.中国民政医学杂志,1997,9(3):146-147.
    [15] Mogi M, Harada M, Narabayashi H, et al. Interleukin (IL)-1 beta, IL-2, IL-4, IL-6 and transforming growth factor-alpha levels are elevated in ventricular cerebrospinal fluid in juvenile parkinsonism and Parkinson's disease. Neurosci Lett, 1996, 211 (1) : 13-16.
    [16] Mogi M, Harada M, Riederer P, et al. Tumor necrosis factor-alpha (TNF-alpha) increases both in the brain and in the cerebrospinal fluid from parkinsonian patients. Neurosci Lett, 1994, 165 (1-2) : 208-210.
    [17] Snyder SH, Sabatini DM, Lai MM, et al. Neural actions of immunophilin ligands. Trends Pharmacol Sci, 1998, 19 (1) : 21-26.
    [18] 程晓馨,李丰桥,黄敏,等.雷公藤氯内酯醇对帕金森病大鼠多巴胺神经元的保护作用.药学学报,2002,37(5):339-342.
    [19] 赵焕英,苏月,杨秋慧,等.6-OHDA纹状体内注射制作大鼠帕金森病模型的实验研究.中国组织化学与细胞化学杂志,2003,12(1):16-21.
    [20] 金惠铭.《病理生理学》.人民卫生出版社,2001,9:178-179.
    [21] Dawson VL, Dawson TM, et al. Nitric oxide actions in neurochemistry. Neurochem Int, 1996, 29 (2) : 97-110.
    [22] Agid Y. Aging, disease and nerve cell death. Bull Acad Natl Med, 1995, 179 (6) : 1193-1203.
    [23] Gorman AM, McGowan A, O'Neill C, et al. Oxidative stress and apoptosis in neurodegeneration. J Neurol Sci, 1996, 139(Suppl): 45-52.
    [24] Offen D, Ziv I, Gorodin S, et al. Dopamine-induced programmed cell death in mouse thymocytes. Biochim Biophys Acta, 1995, 1268(2): 171-177.
    [25] Desole MS, Sciola L, Delogu MR, et al. Manganese and 1-methyl-4- (2' -ethylphenyl)-1, 2, 3, 6-tetrahydropyridine induce apoptosis in PC12 cells. Neurosci Lett, 1996, 209(3): 193-196.
    [26] (?) S, Egensperger R, von Eitzen U, et al. On the question of apoptosis in the parkinsonian substantia nigra. Acta Neuropatho1 (Berl), 1997, 93 (2): 105-108.
    [27] Anglade P, Vyas S, Javoy-Agid F, et al. Apoptosis and autophagy in nigral neurons of patients with Parkinson's disease. Histol Histopathol, 1997, 12(1): 25-31.
    [28] Walkinshaw G, Waters CM, et al. Induction of apoptosis in catecholaminergic PCl2 cells by L-DOPA. Implications for the treatment of Parkinson's disease. J Clin Invest, 1995, 95(6): 2458-2464.
    [29] Zuch CL, Nordstroem VK, Briedrick LA, et al. Time course of degenerative alterations in nigral dopaminergic neurons following a 6-hydroxydopamine lesion. J Comp Neurol, 2000, 427(3): 440-454.
    [30] Jenner PG, Brin MF. Levodopa neurotoxicity: experimental studies versus clinical relevance. Neurology, 1998,50(6 Suppl 6):S39-43, discussion S44-8.
    [31] Junn E, Mouradian MM, et al. Apoptotic signaling in dopamine-induced cell death: the role of oxidative stress, p38 mitogen-activated protein kinase, cytochrome c and caspases. J Neurochem, 2001, 78(2): 374-383.
    [32] Ziv I, Melamed E, Nardi N, et al. Dopamine induces apoptosis-like cell death in cultured chick sympathetic neurons--a possible novel pathogenetic mechanism in Parkinson's disease. Neurosci Lett, 1994, 170(1): 136-140.
    [33] Matsubara K, Senda T, Uezono T, et al.L-Deprenyl prevents the cell hypoxia induced by dopaminergic neurotoxins, MPP(+) and beta-carbolinium: a microdialysis study in rats. Neurosci Lett, 2001, 302(2-3): 65-68.
    [34] Zappia M, Crescibene L, Bosco D, et al. Anti-GM1 ganglioside antibodies in Parkinson's disease. Acta Neuro1 Scand, 2002, 106(1): 54-57.
    [35] Chen S, Le WD, Xie WJ, et al. Experimental destruction of substantia nigra initiated by Parkinson disease immunoglobulins. Arch Neuro1, 1998, 55 (8): 1075-1080.
    [36] Moussa BH, Youdim, Peter Riederer, et al. 对帕金森病的认识,科学(scientific American 中文版),1997, 5: 7-14.
    [37] McGeer EG, McGeer PL, et al. Inflammatory cytokines in the CNS. CNS Drugs, 1997, 7: 214-228.
    [38] Kurkowska-Jastrzebska I, Wrońska A, Kohutnicka M, et al. MHC class II positive microglia and lymphocytic infiltration are present in the substantia nigra and striatum in mouse model of Parkinson's disease. Acta Neurobiol Exp (Wars), 1999, 59(1): 1-8.
    [39] Kim WG, Mohney RP, Wilson B, et al. Regional difference in susceptibility to lipopolysaccharide-induced neurotoxicity in the rat brain: role of microglia. J Neurosci, 2000, 20(16): 6309-6316.
    [40] Chang Re, Hudson P, Wilson B, et al. Influence of neurons on lipopolysaccharide-stimulated production of nitric oxide and tumor necrosis factor-alpha by cultured glia. Brain Res, 2000, 853(2): 236-244.
    [41] Love S. Oxidative stress in brain ischemia. Brain Pathol, 1999, 9(1): 119-131.
    [42] Huang R, Sochocka E, Hertz L, et al. Cell culture studies of the role of elevated extracellular glutamate and K+ in neuronal cell death during and after anoxia/ischemia. Neurosei Biobehav Rev, 1997, 21(2): 129-134.
    [43] Brosnan CF, Battistini L, Raine CS, et al. Reactive nitrogen intermediates in human neuropathology: an overview. Dev Neurosci, 1994, 16(3-4): 152-161.
    [44] Luk JM, Tam P, Fan ST, et al. Immunosuppressive effects of Tripterygium wilfordii polysaccharide on LPS-stimulated human monocytes. Transplant Proc, 2000, 32 (7) : 2013-2015.
    [45] Lee GI, Ha JY, Min KR, et al. Inhibitory effects of Oriental herbal medicines on IL-8 induction in lipopolysaccharide-activated rat macrophages. Planta Med, 1995, 61 (1) : 26-30.
    [46] 李文伟.帕金森病的中药治疗和现代药理研究.现代康复 2000,4(3):338-339.
    [47] 袁灿兴,胡建华.滋补肝肾、通络解毒法治疗帕金森病30例.上海中医药杂志,2004,38(8):8-9.
    [48] 祝维峰,罗荣敬,周丽萍,等.震颤宁治疗帕金森病的实验研究.广州中医药大学学报,2004,21(4):284-287.
    [1] Ziv I, Melamed E, Nardi N, et al. Dopamine induces apoptosis-like cell death in cultured chick sympathetic neurons—a possible novel pathogenetic mechanism in Parkinson's disease. Neurosci Lett, 1994, 70 (1) : 136-140.
    [2] Zilkha-Falb R, Ziv I, Nardi N, et al. Monoamine-induced apoptotic neuronal cell death. Cell Mol Neurobiol, 1997, 17 (1) : 101-118.
    [3] Masserano JM, Gong L, Kulaga H, et al. Dopamine induces apoptotic cell death of a catecholaminergic cell line derived from the central nervous system. Mol Pharmacol, 1996, 50 (5) : 1309-1315.
    [4] Gabby M, Tauber M, Porat S, et al. Selective role of glutathione in protecting human neuronal cells from dopamine-induced apoptosis. Neuropharmacology, 1996, 35 (5) : 571-578.
    [5] Offen D, Ziv I, Gorodin S, et al. Dopamine-induced programmed cell death in mouse thymocytes. Biochim Biophys Acta, 1995, 1268 (2) : 171-177.
    [6] Offen D, Ziv I, Panet H, et al. Dopamine-induced apoptosis is inhibited in PC12 cells expressing Bcl-2. Cell Mol Neurobiol, 1997, 17 (3) : 289-304.
    [7] Ziv I, Offen D, Haviv R, et al. The proto-oncogene Bcl-2 inhibits cellular toxicity of dopamine: possible implications for Parkinson's disease. Apoptosis, 1997, 2 (2) : 149-155.
    [8] Barzilai A, Zilkha-Falb R, Daily D, et al. The molecular mechanism of dopamine-induced apoptosis: identification and characterization of genes that mediate dopamine toxicity. J Neural Transm Suppl, 2000(60): 59-76.
    [9] Junn E, Mouradian MM, et al. Apoptotic signaling in dopamine-induced cell death: the role of oxidative stress, p38 mitogen-activated protein kinase, cytochrome c and caspases. J Neurochem, 2001, 78(2): 374-383.
    [10] Daily D, Barzilai A, Offen D, et al. The involvement of p53 in dopamine-induced apoptosis of cerebellar granule neurons and leukemic cells overexpressing p53. Cell Mol Neurobiol, 1999, 19(2): 261-276.
    [11] Takai N, Nakanishi H, Tanabe K, et al. Involvement of caspase-like proteinases in apoptosis of neuronal PC12 cells and primary cultured microglia induced by 6-hydroxydopamine. J Neurosci Res, 1998, 54(2): 214-222.
    [12] Andersen JK, et al. Does neuronal loss in Parkinson' s disease involve programmed cell death? Bioessays, 2001, 23(7): 640-646.
    [13] Blum D, Torch S, Lambeng N, et al. Molecular pathways involved in the neurotoxicity of 6-OHDA, dopamine and MPTP: contribution to the apoptotic theory in Parkinson' s disease. Prog Neurobiol, 2001, 65(2): 135-172.
    [14] Blum D, Wu Y, Nissou MF, et al. p53 and Bax activation in 6-hydroxydopamine-induced apoptosis in PC12 cells. Brain Res, 1997, 751(1): 139-142.
    [15] von Coelln R, Kügler S, (?) M, et al. Rescue from death but not from functional impairment: caspase inhibition protects dopaminergic cells against 6-hydroxydopamine-induced apoptosis but not against the loss of their terminals. J Neurochem, 2001, 77(1): 263-273.
    [16] Ricaurte GA, Langston JW, Delanney LE, et al. Fate of nigrostriatal neurons in young mature mice given 1-methyl-4-pheny1-1, 2, 3,6-tetrahydropyridine: a neurochemi cal and morphological reassessment. Brain Res, 1986, 376(1): 117-124.
    [17] Petroske E, Meredith GE, Callen S, et al. Mouse model of Parkinsonism: a comparison between subacute MPTP and chronic MPTP/probenecid treatment. Neuroscience, 2001, 106(3): 589-601.
    [18] Fall CP, Bennett JP Jr, et al. Characterization and time course of MPP+ -induced apoptosis in human SH-SY5Y neuroblastoma cells. J Neurosci Res, 1999, 55(5): 620-628.
    [19] Hartmann A, Hunot S, Michel PP, et al. Caspase-3: A vulnerability factor and final effector in apoptotic death of dopaminergic neurons in Parkinson' s disease. Proc Natl Acad Sci U S A, 2000, 97(6): 2875-2880.
    [20] He Y, Lee T, Leong SK, et al. 6-Hydroxydopamine induced apoptosis of dopaminergic cells in the rat substantia nigra. Brain Res, 2000, 858(1): 163-166.
    [21] Murata LB, Dodson MS, et al. The herpes simplex virus type 1 origin-binding protein, sequence-specific activation of adenosine triphosphatase activity by a double-stranded DNA containing box I. J Biol Chem, 1999, 274(52): 37079-37086.
    [22] Tatton NA, Kish SJ, et al. In situ detection of apoptotic nuclei in the substantia nigra compacta of 1-methyl-4-phenyl-1, 2, 3, 6- tetrahydropyridine-treated mice using terminal deoxynucleotidyl transferase labelling and acridine orange staining. Neuroscience, 1997, 77(4): 1037-1048.
    [23] Cosi C, Colpaert F, Koek W, et al. Poly(ADP-ribose) polymerase inhibitors protect against MPTP-induced depletions of striatal dopamine and cortical noradrenaline in C57B1/6 mice. Brain Res, 1996,729(2): 264-269.
    [24] Nishi K. Expression of c-Jun in dopaminergic neurons of the substantia nigra in 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-treated mice. Brain Res, 1997, 771(1): 133-141.
    [25] Saporito MS, Thomas BA, Scott RW, et al. MPTP activates c-Jun NH(2)-terminal kinase (JNK) and its upstream regulatory kinase MKK4 in nigrostriatal neurons in vivo. J Neurochem, 2000, 75(3): 1200-1208.
    [26] Saporito MS, Brown EM, Miller MS, et al. CEP-1347/KT-7515, an inhibitor of c-jun N-terminal kinase activation, attenuates the 1-methyl-4-phenyl tetrahydropyridine-mediated loss of nigrostriatal dopaminergic neurons In vivo. J Pharmacol Exp Ther, 1999, 288(2): 421-427.
    [27] Vila M, Jackson-Lewis V, Vukosavic S, et al. Bax ablation prevents dopaminergic neurodegeneration in the 1-methyl- 4-phenyl-1, 2, 3, 6- tetrahydropyridine mouse model of Parkinson' s disease. Proc Natl Acad Sci U S A, 2001, 98(5): 2837-2842.
    [28] (?) S, Egensperger R, von Eitzen U, et al. On the question of apoptosis in the parkinsonian substantia nigra. Acta Neuropathol (Berl), 1997, 93(2): 105-108.
    [29] Banati RB, Daniel SE, Blunt SB, et al. Glial pathology but absence of apoptotic nigral neurons in long-standing Parkinson's disease. Mov Disord, 1998, 13(2): 221-227.
    [30] Mochizuki H, Goto K, Mori H, et al. Histochemical detection of apoptosis in Parkinson' s disease. J Neurol Sci, 1996, 137(2): 120-123.
    [31] Tatton NA, Maclean-Fraser A, Tatton WG, et al.A fluorescent double-labeling method to detect and confirm apoptotic nuclei in Parkinson's disease. Ann Neurol, 1998, 44(3 Supp1 1):S142-S148.
    [32] de la Monte SM, Sohn YK, Ganju N, et al. P53- and CD95-associated apoptosis in neurodegenerative diseases. Lab Invest, 1998, 78(4): 401-411.
    [33] Andersen JK. Does neuronal loss in Parkinson's disease involve programmed cell death? Bioessays, 2001, 23(7): 640-646.
    [34] Marshall KA, Daniel SE, Cairns N, et al. Upregulation of the anti-apoptotic protein Bcl-2 may be an early event in neurodegeneration: studies on Parkinson's and incidental Lewy body disease. Biochem Biophys Res Commun, 1997, 240(1): 84-87.
    [35] Nagatsu T. Parkinson's disease: changes in apoptosis-related factors suggesting possible gene therapy. J Neural Transm, 2002, 109(5-6): 731-745.
    [36] Mogi M, Nagatsu T, et al. Neurotrophins and cytokines in Parkinson's disease. Adv Neurol, 1999, 80: 135-139.
    [37] Gelowitz DL, Paterson IA, et al. Neuronal sparing and behavioral effects of the antiapoptotic drug, (-)deprenyl, following kainic acid administration. Pharmacol Biochem Behav, 1999, 62(2): 255-262.
    [38] Saporito MS, Brown EM, Miller MS, et al. CEP-1347/KT-7515, an inhibitor of c-jun N-terminal kinase activation, attenuates the l-methyl-4-phenyl tetrahydropyridine-mediated loss of nigrostriatal dopaminergic neurons In vivo. J Pharmacol Exp Ther, 1999, 288(2): 421-427.
    [39] Woodgate A, MacGibbon G, Walton M, et al. The toxicity of 6-hydroxydopamine on PC12 and P19 cells. Brain Res Mol Brain Res, 1999, 69(1): 84-92.
    [1] Fearnley JM, Lees AJ. Ageing and Parkinson's disease: substantia nigra regional selectivity. Brain, 1991, 114 (5) : 2283-2301.
    [2] Kitayama S, Shimada S, Uhl GR, et al. Parkinsonism-inducing neurotoxin MPP+: uptake and toxicity in nonneuronal COS cells expressing dopamine transporter cDNA. Ann Neurol, 1992, 32 (1) : 109-111.
    [3] Tissingh G, Bergmans P, Booij J, et al. Drug-naive patients with Parkinson's disease in Hoehn and Yahr stages Ⅰ and Ⅱ show a bilateral decrease in striatal dopamine transporters as revealed by [123I]beta-CIT SPECT. J Neurol, 1998, 245 (1) : 14-20.
    [4] Huang WS, Lin SZ, Lin JC, et al. Evaluation of early-stage Parkinson's disease with 99mTc-TRODAT-1 imaging. J Nucl Med, 2001, 42 (9) : 1303-1308.
    [5] Faraj BA, Olkowski ZL, Jackson RT, et al. Binding of [3H]-dopamine to human lymphocytes: possible relationship to neurotransmitter uptake sites. Pharmacology, 1991, 42 (3) : 135-141.
    [6] Caronti B, Antonini G, Calderaro C, et al. Dopamine transporter immunoreactivity in peripheral blood lymphocytes in Parkinson's disease. J Neural Transm, 2001, 108 (7) : 803-807.
    [7] 张璟,肖勤,陈生弟,等.帕金森病患者血淋巴细胞多巴胺转运蛋白功能与密度的研究.诊断学理论与实践,2004,3(2):79-82.
    [8] Leenders KL, Salmon EP, Tyrell P, et al. The nigrostriatal dopamic system assessed in vivo by positron emissiontomography in health volunteer subjects and patients with Parkinson's disease. Arch Neurol 1990, 47: 1290-1298.
    [9] Mogi M, Togari A, Kondo T, et al. Brain-derived growth factor and nerve growth factor concentrations are decreased in the substantia nigra in Parkinson's disease. Neurosci Lett, 1999, 270 (1) : 45-48.
    [10] Jankovic J. New and emerging therapies for Parkinson disease. Arch Neurol, 1999, 56(7): 785-790.
    [11] Chiba S, Matsumoto H, Saitoh M, et al. A correlation study between serum adenosine deaminase activities and peripheral lymphocyte subsets in Parkinson's disease. J Neurol Sci, 1995, 132(2): 170-173.
    [12] Bas J, Calopa M, Mestre M, et al. Lymphocyte populations in Parkinson's disease and in rat models of parkinsonism. J Neuroimmunol, 2001, 113(1): 146-152.
    [13] Fiszer U. Study of the immunologic status of persons with Parkinson disease with special reference to the effect of levodopa treatment. Preliminary report. Neurol Neurochir Pol, 1989, 23(1): 7-11.
    [14] Fiszer U, Mix E, Fredrikson S, et al. Parkinson's disease and immunological abnormalities: increase of HLA-DR expression on monocytes in cerebrospinal fluid and of CD45RO+T cells in peripheral blood. Acta Neurol Scand, 1994, 90(3): 160-166.
    [15] Barbanti P, Fabbrini G, Ricci A, et al. Increased expression of dopamine receptors on lymphocytes in Parkinson's disease. Mov Disord, 1999, 14(5):764-771.
    [16] Giros B, el Mestikawy S, Godinot N, et al. Cloning, pharmacological characterization, and chromosome assignment of the human dopamine transporter. Mol Pharmacol, 1992, 42(3): 383-390.
    [17] Donovan DM, Vandenbergh DJ, Perry MP, et al. Human and mouse dopamine transporter genes: conservation of 5'-flanking sequence elements and gene structures. Brain Res Mol Brain Res, 1995, 30(2): 327-335.
    [18] Shimada S, Kitayama S, Lin CL, et al. Cloning and expression of a cocaine-sensitive dopamine transporter complementary DNA. Science, 1991 254(5031): 576-578.
    [19] Cerruti C, Walther DM, Kuhar MJ, et al. Dopamine transporter mRNA expression is intense in rat midbrain neurons and modest outside midbrain. Brain Res Mol Brain Res, 1993, 18(1-2): 181-186.
    [20] Kaufman MJ, Madras BK, et al. Severe depletion of cocaine recognition sites associated with the dopamine transporter in Parkinson's-diseased striatum. Synapse, 1991, 9 (1) : 43-49.
    [21] Seibyl JP, Marek KL, Quinlan D, et al. Decreased single-photon emission computed tomograpbic [123I]beta-CIT striatal uptake correlates with symptom severity in Parkinson's disease. Ann Neurol, 1995, 38 (4) : 589-598.
    [22] Guttman M, Burkholder J, Kish SJ, et al. [11C]RTI-32 PET studies of the dopamine transporter in early dopa-naive Parkinson's disease: implications for the symptomatic threshold. Neurology, 1997, 48 (6) : 1578-1583.
    [23] Innis RB, Marek KL, Sheff K, et al. Effect of treatment with L-dopa/carbidopa or L-selegiline on striatal dopamine transporter SPECT imaging with [123I]beta-CIT. Mov Disord, 1999, 14 (3) : 436-442.
    [24] 杨莉芹,蒋雨平,王坚,等.治疗帕金森病的不同药物对基底节多巴胺能系统的影响.中国临床神经科学,2005,13(2):111-117.
    [25] Parkinson Study Group. Dopamine transporter brain imaging to assess the effects of pramipexole vs levodopa on Parkinson disease progression. JAMA, 2002, 287 (13) : 1653-1661.
    [1] Fearnley JM, Lees AJ. Ageing and Parkinson's disease: substantia nigra regional selectivity. Brain, 1991, 114: 2283-2301.
    [2] Clarke CE, Guttman M. Dopamine agonist monotherapy in Parkinson's disease. Lancet, 2002, 360: 1767-1769.
    [3] Moroi K, Hsu LL. A brain synaptic dopamine-binding protein: isolation and partial characterization. J Neurosci Res, 1984, 12: 113-128.
    [4] Seeman P, Niznik HB. Dopamine receptors and transporters in Parkinson's disease and schizophrenia. FASEB J, 1990, 4: 2737-2744.
    [5] Huang WS, Lin SZ, Lin JC, et al. Evaluation of early-stage Parkinson's disease with 99mTc-TRODAT-1 imaging. J Nucl Med, 2001, 42: 1303-1308.
    [6] Faraj BA, Olkowski ZL, Jackson RT, et al. Binding of [3H]-dopamine to human lymphocytes: possible relationship to neurotransmitter uptake sites. Pharmacology, 1991, 42: 135-141.
    [7] Bergquist J, Tarkowski A, Ekman R, et al. Discovery of endogenous catecholamines in lymphocytes and evidence for catecholamine regulation of lymphocyte function via an autocrine loop. Proc Natl Acad Sci, 1994, 91: 12912-12916.
    [8] Bahjat A, Faraj BA, Zbigniew L, et al. A cocaine-sensitive active dopamine transport in human lymphocytes. Biochemical Pharmacology, 1995, 50: 1007-1014.
    [9] Nagai Y, Ueno S, Saeki Y, et al. Decrease of the D3 dopamine receptor mRNA expression in lymphocytes from patients with Parkinson's disease. Neurology, 1996, 46: 791-795.
    [10] Barbanti P, Fabbrini G, Ricci A, et al. Increased expression of dopamine receptors on lymphocytes in Parkinson's disease. Mov Disord, 1999, 14: 764-771.
    [11] Caronti B, Tanda G, Colosimo C, et al. Reduced dopamine in peripheral blood lymphocytes in Parkinson's disease. Neuroreport, 1999, 10: 2907.
    [12] Caronti B, Antonini G, Calderaro C, et al. Dopamine transporter immunoreactivity in peripheral blood lymphocytes in Parkinson' s disease. J Neural Transm, 2001, 108: 803-807.
    [13] Krieger K, Klimke A, Henning U, et al. Active [3H]-dopamine uptake displayed by native lymphocyte suspensions is mainly due to contaminating platelets. Pharmacopsychiatry, 1998, 31: 193-198.
    [14] Amenta F, Bronzetti E, Cantalamessa F, et al. Identification of dopamine plasma membrane and vesicular transporters in human peripheral blood lymphocytes. J Neuroimmunol, 2001, 117: 133-142.
    [15] Weihe E, Bette M, Fink T, et al. Molecular anatomical basis of interactions between nervous and immune systems in health and disease. Psychoneuroimmunology, 1999: 167-183.
    [16] Faraj BA, Olkowski ZL, Jackson RT, et al. Expression of a high-affinity serotonin transporter in human lymphocytes. Int J Immunopharmacol, 1994, 16: 561-567.
    [17] (?) N, Urbina M, Obregó F, et al. Characterization of serotonin transporter in blood lymphocytes of rats. Modulation by in vivo administration of mitogens. J Neuroimmunol, 2005, 159: 31-40.

© 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