摘要
目的探讨细胞凋亡在帕金森病发病机制中的作用。方法给Ｃ５７ＢＬ小鼠腹腔注射不同剂量、不同时限的１甲基４苯基１，２，３，６四氢吡啶（ＭＰＴＰ），在用ＭＰＴＰ之前，给Ｃ５７ＢＬ小鼠口服咪多吡（Ｅｌｄｅｐｒｙｌ）或Ｒｉｌｕｚｏｌｅ，分别用ＤＮＡ末端标记法（ＴＵＮＥＬ）和流式细胞术（ＦＡＣＳ）对小鼠黑质细胞检测凋亡，并用同样方法检测分别用等浓度的１甲基４苯基吡啶离子（ＭＰＰ＋）及ＭＰＴＰ处理的ＰＣ１２细胞。结果３０ｍｇ／ｋｇ体重ＭＰＴＰ连续应用３天以上诱发黑质细胞凋亡，而１０ｍｇ／ｋｇ体重ＭＰＴＰ无致凋亡作用。咪多吡预处理可防止ＭＰＴＰ诱发的黑质细胞凋亡；Ｒｉｌｕｚｏｌｅ能减轻ＭＰＴＰ诱发的黑质细胞凋亡程度。２０μｍｏｌ／Ｌ浓度的ＭＰＰ＋使ＰＣ１２细胞发生凋亡，等浓度的ＭＰＴＰ对ＰＣ１２细胞无致凋亡作用。结论帕金森病发病机制可能与细胞凋亡有关。ＭＰＴＰ在体内转化为ＭＰＰ＋导致黑质细胞凋亡。
Objective To investigate the possible role of apoptosis in the pathogenesis of Parkinson disease. Method C57 BL mice were intraperitoneally treated with different dosages and different durations of MPTP. And C57 BL mice were orally pretreated with Eldepryl or Riluzole 30 minutes or 60 minutes prior to MPTP.Then TUNEL and FACS analyses of neuronal apoptosis in the substantia nigra were performed on all mice. The same methods were used to test PC12 cell lines, which were treated with MPP+,MPTP or PBS.Results Consecutive treatment of 30 mg/kg MPTP for three days or longer induced apoptosis in neurons of substantia nigra. Whereas lowerdosage of MPTP(10 mg/kg) did not induce apoptosis. MPTPinduced nigral apoptosis could be completely prevented by pretreatment of Eldepryl. Riluzole, to a lesser extent, could reduce the MPTPinduced nigral apoptosis. 20 μmol/L concentration of MPP+ led to apoptosis of PC12 cells, while the same concentration of MPTP had no such effect on PC12 cells. Conclusion Nigral neuronal apoptosis may be involved in the pathogenesis of Parkinson disease and the apoptotic effect of MPTP in vivo on the nigral neurons is realized through its intermediate MPP+.
出处
《中华神经科杂志》
CAS
CSCD
1998年第4期216-219,共4页
Chinese Journal of Neurology
基金
上海市卫生系统"百人"跨世纪优秀学科带头人培养计划和国家教育部留学回国人员基金
关键词
帕金森病
细胞凋亡
咪多吡
实验
Parkinson disease Apoptosis 1methyl4phenyl1,2,3,6tetrahydropyridine 1methyl4phenylpyridinium Eldepryl Riluzole
