低分子肝素对MPTP帕金森小鼠的治疗作用及可能机制

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／kgx7d）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（1501U／kg·12hx7d）。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。

Therapeutic effect of low molecular weight heparin in MPTP-treated mice and a possible mechanism

Objective： To investigate the therapeutic effect of low molecular weight heparin in MPTP-induced mouse model of Parkinson＇s disease and its possible mechanism. Methods： C57BL mice were randomly divided into 3 groups.MPTP group were intraperitoneally injected with MPTP at the dose of 30mg/kg for 7 days.Low molecular weight heparin＋MPTP group were treated with MPTP （30mg/kg）together with low molecular weight heparin （ 150IU/kg. 12h~ 7d）for 7 days.Normal control group received normal saline correspondently. The behavioral changes in different groups were observed by pole tests .TyrosineHydroxylase （TH） positive cells were detected by immunohistochemistry,and microglia was dete6ted by silver stain. Results： Low molecular weight heparin ＋MPTP group did better than the MPTP group in the behavioral tests and presented less involuntary movements.The quantity of TH positive cells was larger in the low molecular weight heparin ＋MPTP group.The morphology of microglia seemed activated in the MPTP group. Conclusions： Low molecular weight heparin has a neuroprotective effect for preventing dopaminergic neurons from inpariment by MPTP. The mechanism may be related to the modulation of microglia activation. K