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目的:研究1-甲基-4-苯基-1,2,3,6-四氢吡啶(1-methy-4-phenyl-1,2,3,6-tetrahy-dropyridine,MPTP)帕金森病(PD)模型中小胶质细胞的激活情况,探讨低分子肝素对MPTP导致的小胶质细胞活化的抑制作用。方法:C57BL随机分成正常对照组、MPTP组、低分子肝素+MPTP组。MPTP组腹腔注射MPTP(30mg/kg×7d)同时腹部皮下注射生理盐水,低分子肝素+MPTP组在注射MPTP同时腹部皮下注射低分子肝素(150IU/kg·12h×7d)。各组于末次给药后予行为学测试,7d后免疫组化检测酪氨酸羟化酶(TyrosineHydroxylase,TH)阳性细胞。镀银染色观察小胶质细胞激活情况。结果:MPTP组较低分子肝素+MPTP组爬竿时间明显延长,并出现更多非随意动作。低分子肝素+MPTP组黑质部位TH阳性细胞数量高于MPTP组。MPTP组活化的小胶质细胞数量高于低分子肝素+MPTP组。结论:低分子肝素通过抑制小胶质细胞的激活减少MPTP帕金森小鼠多巴胺能神经元的损伤,提示低分子肝素可能有延缓PD进程的作用。
Objective: To investigate the effect of 1-methy-4-phenyl-1,2,3,6-tetrahy-dropyridine (MPTP) on Parkinson’s disease (PD) model of microglia in activation of low molecular weight heparin MPTP-induced microglial activation. Methods: C57BL was randomly divided into normal control group, MPTP group and low molecular weight heparin + MPTP group. MPTP group was intraperitoneally injected with MPTP (30mg / kg × 7d) and subcutaneous injection of normal saline. Low molecular weight heparin + MPTP group was subcutaneously injected with low molecular weight heparin (150IU / kg · 12h × 7d). The rats in each group were given behavioral tests after the last administration, and tyrosine hydroxylase (TH) positive cells were detected by immunohistochemistry 7 days later. Silver staining to observe microglia activation. Results: In the MPTP group, the climbing time of lower molecular weight heparin + MPTP group was significantly prolonged and more involuntary movements occurred. The number of TH positive cells in substantia nigra of low molecular weight heparin + MPTP group was higher than that in MPTP group. The number of activated microglia in MPTP group was higher than that in low molecular weight heparin + MPTP group. Conclusion: Low molecular weight heparin can reduce the damage of dopaminergic neurons in MPTP mice by inhibiting microglial activation, suggesting that low molecular weight heparin may delay the progression of PD.