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目的 探讨盐酸多奈哌齐对血管性痴呆小鼠海马CA1区Calpain Ⅰ-Cdk5/p25通路表达的影响.方法 小鼠随机分为假手术组、模型组和盐酸多奈哌齐治疗组.分别于脑缺血-再灌注后第4周、6周和第8周应用免疫组化观察海马CA1区Calpain Ⅰ的表达,Western-blot方法测定Cdk5/p25的表达.结果 术后4周、6周和8周时模型组小鼠海马CA1区Calpain Ⅰ的表达分别为(0.098 ±0.009)、(0.129 ±0.01)、(0.116 ±0.01),显著高于假手术组的(0.03 ±0.003)、(0.031 ±0.003)、(0.029 ±0.003) (P＜ 0.05)；模型组Cdk5的表达为(0.54±0.05)、(0.73±0.07)、(0.7±0.06),假手术组为(0.23±0.02)、(0.31±0.02)、(0.33±0.02),差异有显著性(P＜0.05)；模型组p25的表达分别为(0.44±0.04)、(0.51±0.04)、(0.55±0.06),显著高于假手术组的(0.19 ±0.02)、(0.24 ±0.02)、(0.2±0.02)(P＜0.05).多奈哌齐治疗组小鼠在术后4周、6周和8周时海马CA1区Calpain Ⅰ表达为(0.041 ±0.004)、(0.054 ±0.004)、(0.046±0.003),较模型组显著降低(P＜0.05),Cdk5的表达为(0.28 ±0.02)、(0.33±0.03)、(0.38±0.02),p25的表达为(0.26±0.02)、(0.25±0.03)、(0.21±0.02),分别显著低于模型组小鼠(P＜0.05).结论 盐酸多奈哌齐改善小鼠学习和记忆的能力可能与其降低Calpain Ⅰ-Cdk5/p25通路的表达有关.“,”Objective To investigate the effect of donepezil hydrochloride on the expression of Calpain Ⅰ-Cdk5/p25 pathway in the hippocampal CA1 area by cerebral ischemia and reperfusion in mice.Methods Mice were divided into model group,sham-operated group and donepezil-treated group.The expression of Calpain Ⅰ in hippocampal CA1 area was measured by immunohistochemistry staining respectively at 4,6 and 8 weeks post cerebral ischemia and reperfusion.Western blot was used to evaluate Cdk5 and p25 protein expression.Results The abilities of learning and memory performance was damaged significantly at 4,6 and 8 weeks after surgery compared to sham-operated group (P＜ 0.05).The expression of Calpain Ⅰ of model group were (0.098 ± 0.009),(0.129 ±0.01),(0.116 ± 0.01),which were higher than that of sham-operated group (0.03 ± 0.003),(0.031 ± 0.003),(0.029 ±0.003) and there was significant difference (P ＜ 0.05).The expression of Cdk5 in model group was (0.54 ± 0.05),(0.73 ± 0.07),(0.7 ± 0.06),which were higher than that of sham-operated group (0.23 ±0.02),(0.31 ± 0.02),(0.33 ± 0.02) and there was significant difference (P ＜ 0.05).The expression of p25 in model group was (0.44 ± 0.04),(0.51 ± 0.04),(0.55 ± 0.06),which were higher than that of sham-operated group(0.19 ± 0.02),(0.24 ± 0.02),(0.2 ± 0.02) and there was significant difference (P ＜ 0.05).The expression of Calpain Ⅰ of donepezil-treated group was (0.041 ± 0.004),(0.054 ± 0.004),(0.046 ± 0.003),which were lower than that of model group.The expression of Cdk5 was (0.28 ± 0.02),(0.33 ± 0.03),(0.38 ± 0.02),and expression of p25 was (0.26 ± 0.02),(0.25 ± 0.03),(0.21 ± 0.02),which were lower than that of model group respectively(P ＜ 0.05).Conclusion Donepezil hydrochloride probably improve the learning and memory abilities by reducing the expression of Calpain Ⅰ and Cdk5/p25.