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鱼藤酮对慢性帕金森病小鼠中脑黑质致密部α-突触核蛋白表达的影响

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Keywords: 帕金森病,黑质,鱼藤酮,突触核蛋白

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Abstract:

目的?观察长期小剂量鱼藤酮暴露对C57BL小鼠行为学和中脑黑质区病理学的改变,并观察鱼藤酮对中脑黑质区α-?突触核蛋白(α-syn)表达的影响。方法??将雄性C57BL小鼠随机分为鱼藤酮组(n=14)和对照组(n=10)。鱼藤酮组给予背部皮下注射鱼藤酮1mg/kg,1次/d,连续注射40d;对照组经相同方式给予相同体积的DMSO和生理盐水混合液。采用自由活动实验和游泳实?验评价小鼠的行为学改变。免疫组化法检测小鼠中脑黑质致密部酪氨酸羟化酶(TH)和α-syn的表达,RT-PCR检测α-synmRNA的?表达情况。结果??行为学观察发现,鱼藤酮组自由活动实验和游泳实验显示,末次给药后3d鱼藤酮组和对照组小鼠穿梭距离分别为165.4±5.5、257.6±4.6格,下肢站立次数分别为20.3±3.3、34.9±3.5次;游泳实验活动能力评分分别为1.8±0.4、2.8±0.2;两组间?差异均有统计学意义(P<0.05)。免疫组化检测发现,鱼藤酮组TH阳性细胞计数(18.5±4.0个)比对照组(24.2±2.4个)明显减少(P<0.05)。鱼藤酮组中脑黑质部存在α-syn阳性包涵体,且α-syn阳性细胞的积分光密度值(2160.00±86.20)较对照组(1698.00±?78.22)明显增加(P<0.01)。结论??慢性鱼藤酮中毒能诱导C57BL小鼠发生PD样的行为学和病理学改变,导致中脑黑质TH阳性多巴胺能神经元减少,促使α-syn表达增高并聚集。

References

[1]  Chesselet MF, Fleming S, Mortazavi F, et al . Strengths and limita-tions of genetic mouse models of Parkinson''s disease[J]. Parkinsonism Relat Disord, 2008, 14(Suppl 2): S84-S87.[2] Dauer W, Kholodilov N, Vila M, et al . Resistance of alpha-synucle-in null mice to the parkinsonian neurotoxin MPTP[J]. Proc Natl Acad Sci USA, 2002, 99(22): 14524-14529.[3] Inden M, Kitamura Y, Takeuchi H, et al . Neurodegeneration of mouse nigrostriatal dopaminergic system induced by repeated oral ad-ministration of rotenone is prevented by 4-phenylbutyrate, a chemical chaperone[J]. Neurochem, 2007, 101(6): 1491-1504.[4] Fornaguera J, Schwarting RK. Early behavioral changes after nigro-striatal system damage can serve as predictors of striatal dopamine de-pletion[J]. Prog Neuropsychopharmacol Biol Psychiatry, 1999, 23(8): 1353-1368.[5] Donnan GA, Willis GL, Kaczmarczyk SJ, et al . Motor function in the 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine-treated mouse[J]. Neurol Sci, 1987, 77(2-3): 185-191.[6] Sun F, Kanthasamy A, Anantharam V, et al . Environmental neuro-toxic chemicals-induced ubiquitin proteasome system dysfunction in the pathogenesis and progression of Parkinson''s disease[J]. Pharma-col Ther, 2007, 114(3): 327-344.[7] Meredith GE, Sonsalla PK, Chesselet MF. Animal models of Par-kinson''s disease progression[J]. Acta Neuropathol, 2008, 115(4): 385-398.[8] Beal MF. Experimental models of Parkinson''s disease[J]. Nat Rev Neurosci, 2001, 2(5): 325-334.[9]尹丰,田增民,刘爽,等.神经细胞移植对帕金森病大鼠模型的治疗作用观察[J].解放军医学杂志, 2008, 33(9): 1113-1116.[10]赵喜林,顾振纶,秦正红,等,长期低剂量皮下注射鱼藤酮制作大鼠帕金森病模型.中国药理学通报[J], 2005, 21(10): 1274-1277.[11]高云朝,林祥通. MPTP帕金森病动物模型研究进展[J].中国实验动物学报, 2005, 13(4): 261-265.[12] Thiffault C, Langston JW, Di Monte DA. Increased striatal dopa-mine turnover following acute administration of rotenone to mice[J]. Brain Res, 2000, 885(2): 283-288.[13]戚辰,刘振国,范国华,等.鱼藤酮对多巴胺能神经元的神经毒性作用[J].中华神经科杂志, 2004, 37(6): 538-542.[14] Friedrich T, van Heek P, Leif H, et al . Two binding sites of inhibi-tors in NADH: ubiquinone oxidoreductase(complex I). Relationship of one site with the ubiquinone-binding site of bacterial glucose:ubiquinone oxidoreductase. Eur J Biochem, 1994, 15(1-2): 691-698.[15] Cookson MR, van der Brug M. Cell systems and the toxic mechanism(s) of alpha-synuclein[J]. Exp Neurol, 2008, 209(1): 5-11.[16]陈涛,唐北沙,廖小平.α-突触核蛋白在帕金森病发病机制中的作用[J].中华神经科杂志, 2006, 39(6): 415-418.[17]王少君,王加才,彭国光,等.含CpG基元核酸疫苗免疫慢性MPTP帕金森病小鼠的治疗作用[J].中国实验动物学报, 2008, 16(3): 179-182.

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