双他克林对原代培养小鼠星形胶质细胞缺氧缺糖损伤的保护作用

Protection against anoxic and glucose-deprived injury in primary cultured mouse astrocytes by bis(7)-tacrine

目的 :研究一种新的乙酰胆碱酯酶抑制剂双他克林在缺氧、缺糖诱导的细胞坏死和细胞凋亡中的作用。方法 :用缺氧和缺糖来诱导原代培养的小鼠大脑皮层星形胶质细胞损伤 ,通过测定 L DH释放量观察细胞存活率 ;相差显微镜和 Hoechst 33342染色观察细胞和核形态 ,并计数核固缩的细胞数量。结果 :缺氧、缺糖 6 h后约 6 0～ 70 %的细胞发生凋亡 ,使用双他克林 (1- 10 n M)可有效抑制缺氧、缺糖诱导的细胞凋亡 ,从形态学和生化检测两方面均可证实这一结果。结论 :双他克要可保护星形胶质细胞免受缺氧、缺糖性损伤。提示除了 AD外 。

Objective:To study the effects of bis(7) tacrine, a novel acetylcholinesterase inhibitor, on ischemicinduced cell death and apoptosis in primary cerebral cortical astrocytes of mice. Methods: Percentage of viable cells was observed by lactate dehydrogenase (LDH) release assay. Furthermore, in situ TdT mediated dUTP nick end labeling (TUNEL) and Hoechst 33342 double labeling method was employed, allowig the simultaneous identification of condensed muclei and DNA fragmentation in the astrocytes. Results: Following a 6h in vitro ischemic incubation of the cultures, about 60 70% of the cells underwent apoptosis. Treatment with bis(7) tacrine (1 10nM) during ischemic incubartion effectively inhibited the ischemic induced apoptosis, as demonstrated by morphological and biochemical tests. Conclusion: Our results demonstrated that bis (7) tacrine could protect astrocytes against ischemic induced cell injury, indicating that the drug might be beneficial for the reatment of vascular dementia, in addition to Alzheimer's disease.\;