环鸟苷酸依赖性蛋白激酶拮抗酒精性中枢神经细胞毒性机制研究

目的 探讨环鸟苷酸依赖性蛋白激酶对酒精致鼠小脑颗粒细胞(cerebellar granule cells,CGC)毒性作用的影响机制.方法 通过光学显微镜观察一氧化氮(NO)释放剂,环鸟苷酸及环鸟苷酸依赖性蛋白激酶抑制剂对鼠小脑颗粒细胞存活的影响.结果 NO释放剂,环鸟苷酸在无酒精组中促进细胞的生存,并能对CGC产生保护作用,减少酒精对细胞的杀死.环鸟苷酸依赖性蛋白激酶抑制剂可抑制二者对细胞的作用.结论 环鸟苷酸依赖性蛋白激酶在NO释放剂和环鸟苷酸促鼠小脑颗粒细胞的存活和抵抗酒精性神经毒性过程中具有重要的作用.

Role of cGMP-dependent protein kinase against ethanol neurotoxicity of cerebellar granule cells

Objective To analyze the function of cGMP-dependent protein kinase(PKG)in the survival of cultured rat cerebellar granule cells(CGC).Methods CGC culture was incubated for 24 h before addition of ethanol and different reagents,such as Deta-NONOate(a NO donor),Br-cGMP and Rp-8-pCPT-cGMPS(a cGMP-dependent protein kinase inhibitor).After the treatment,samples were incubated for another 24 h,then the cells were collected and counted by using hemocytometer.Results Deta-NONOate and Br-cGMP enhanced the cell survival in the absence of ethanol,indicating their neurotrophic effects.They showed neuroprotective effect on the cultured CGC since they could reduce the ethanol-induced cell death.Inhibiting PKG with Rp-8-pCPT-cGMPS could eliminate both neurotrophic and neuroprotective effects mediated by Deta-NONOate and Br-cGMP.Conclusion cGMP-dependent protein kinase plays a key role in the cultured CGC survival and protects the cells against ethanol neurotoxicity.