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目的探讨慢性脑缺血对大鼠海马α-分泌酶的表达和活性的影响。方法双侧颈总动脉结扎制作大鼠慢性脑缺血模型,分别于术后10 d、30 d、90 d和180 d用Y迷宫测试其学习记忆能力;分别用定量PCR和免疫印迹法检测海马α-分泌酶ADAM 10和ADAM 17m RNA的表达和蛋白含量;用荧光法测定海马α-分泌酶的活性。结果 Y迷宫测试显示模型组术后30 d、90 d和180 d所需的电击次数较对照组逐渐增加(P<0.05;P<0.01)。PCR和免疫印迹结果显示,术后30 d、90 d和180 d海马ADAM 10和ADAM 17m RNA表达及其含量明显降低(P<0.05;P<0.01);酶活性检测显示模型组α-分泌酶活性于术后持续性降低,与对照组相比,差异有统计学意义(P<0.05,P<0.01)。结论慢性脑缺血下调海马α-分泌酶表达,并抑制其活性,可能在阿尔茨海默病发病过程中有重要意义。
Objective To investigate the effects of chronic cerebral ischemia on the expression and activity of α-secretase in the hippocampus of rats. Methods Bilateral common carotid arteries were ligated to make a model of chronic cerebral ischemia in rats. The learning and memory abilities of the rats were tested by Y-maze test at 10 d, 30 d, 90 d and 180 d after operation. The hippocampus α-secretase ADAM 10 and ADAM 17m RNA expression and protein content; Determination of the activity of α-secretase in the hippocampus by fluorescence method. Results The Y maze test showed that the number of shocks required by the model group at 30 d, 90 d and 180 d after operation was significantly higher than that of the control group (P <0.05; P <0.01). The results of PCR and Western blot showed that the expression of ADAM 10 and ADAM 17mRNA in the hippocampus decreased significantly at 30 d, 90 d and 180 d after operation (P <0.05; P <0.01). The activity of α-secretase The activity decreased persistently after operation, and the difference was statistically significant compared with the control group (P <0.05, P <0.01). Conclusion Chronic cerebral ischemia can downregulate the expression of α-secretase in hippocampus and inhibit its activity, which may play an important role in the pathogenesis of Alzheimer’s disease.