中文摘要：

目的探讨ATP敏感的钾离子（KATP）通道开放药物二氮嗪防治A1-42细胞毒性作用的分子机制。方法采用细胞原代培养的方法,培养大鼠皮层神经元并进行鉴定。将原代培养的细胞随机分为对照组、单纯Aβ1-42干预组、二氮嗪预处理1 h后Aβ1-42干预组、单纯二氮嗪预处理组和单纯Aβ42-1干预组（Aβ1-42反序列对照）,各组又分为24、72 h两个亚组。采用免疫荧光双染及免疫印迹法,观察干预后不同培养时间（24、72 h）细胞KATP通道各亚基Kir6.1、Kir6.2、SUR1、SUR2蛋白表达水平的变化。结果与对照组比较,单纯A1-42处理24 h组Kir6.1、SUR2显著升高（P〈0.05）,二氮嗪预处理后Aβ1-42作用细胞24 h组各亚基表达均无明显变化;二氮嗪预处理后Aβ1-42作用细胞72 h组与单纯A1-42处理72 h组KATP通道各亚基表达均明显升高（P〈0.05）,而二氮嗪预处理后Aβ1-42作用细胞72 h组与单纯A1-42处理72 h组相比Kir6.1、Kir6.2、SUR2表达显著下调（P〈0.05）。结论二氮嗪预处理可完全逆转A1-42作用神经元24 h所引起的Kir6.2及SUR1的表达上调,只能部分逆转A1-42作用神经元72 h所引起的Kir6.1、Kir6.2、SUR2的表达增加,可能会维持神经细胞正常生理功能,起到防治A1-42细胞毒性作用。

英文摘要：

Objective To investigate the possible molecular mechanism of mitochondrial ATP-sensitive potassium（KATP） channel opener diazoxide in preventing cytotoxicity of Aβ1-42.Methods Primary neurons were cultured and evaluated by immunocytochemistry.Cells were randomly divided into 5 groups： the control group,the Aβ1-42 group,the diazoxide ＋ Aβ1-42 group,the diazoxide group and the Aβ42-1 group.After treatment for 24 h or 72 h,subunits of KATP（Kir6.1,Kir6.2,SUR1 and SUR2） were detected by double immunofluorescence and immunoblotting.Results ① Being treated with Aβ1-42（2 μmol / L） for 24 h,expressions of Kir6.1 and SUR2 were significantly up-regulated,and the changes could be completely reversed by pretreatment with diazoxide（1mmol / L） for 1 h（P 0.05）.② There were significant increases in all KATP subunit expression levels after exposure to Aβ1-42 for 72 h,and up-regulation of Kir6.1,Kir6.2 and SUR2 except SUR1 could be partly reversed by pretreatment with diazoxide（1 mmol / L） for 1 h（P 0.05）.Conclusion Diazoxide could reverse enhanced expressions of KATP subunits in neurons caused by exposure to Aβ1-42,which may explain,in part,the effect of diazoxide on resistance to the toxicity of Aβ1-42.