目的 观察卡托普利和氯沙坦对血管性痴呆(VD)模型大鼠海马CA1区神经元凋亡和Bcl-2及Bax蛋白表达的影响,探讨卡托普利和氯沙坦抗脑缺血损伤改善VD的作用机制.方法 取SD大鼠,采用不同时间点分别结扎左、右颈总动脉建立VD模型,将建模成功大鼠随机分为卡托普利组(卡托普利,2.5 mg/kg)、氯沙坦组(氯沙坦,2.0 mg/kg)、模型组(生理盐水)和假手术组(生理盐水),每组lo只,灌胃给予相应药物,每天1次,连续给药4w后,用TUNEL法检测各组海马神经元凋亡,用免疫组织化学法检测其Bcl-2及Bax蛋白表达情况.结果 模型组大鼠海马可见大量凋亡神经元；模型组Bcl-2及Bax蛋白表达明显增加,与假手术组比较差异均有显著意义；而卡托普利组和氯沙坦组大鼠凋亡神经元和Bcl-2及Bax蛋白表达有明显改善.结论 卡托普利及氯沙坦均可通过减少海马神经元凋亡,影响Bcl-2及Bax蛋白表达来改善VD模型大鼠学习记忆能力.%Objective To observe the effect of captopril and losartan on neuronal apoptosis, Bcl-2 and the Bax protein expression in hippocampus of vascular dementia ( VD) rats, and study neuroprotection mechanism of them. Methods SD rats were randomly divided into captopril-treated group (kaptopril,2. 5 mg/kg) , losartan-treated group (losartan, 2. 0 mg/kg) , sham-operated group (normal saline) and untreated group (normal saline). The animal models were produced by permanent occlusion in two times operation at 3 days interval of bilateral common carotid arteries of rats. Captopril and losartan were fed to the captopril and losartan-treated groups rats for 4 weeks. TUNEL staining was used to examine neurons apoptosis and the expressions of Bcl-2 and Bax protein in neurons of hippocampal CA1 region were investigated by immunohistochemical method. Results Compared with the model group, the number of neuron apoptosis and the expression of Bax protein in hippocampal of the captopril and losartan-treated groups rats were reduced significantly. Conclusions Captopril and losartan can improve the ability of learning and memory of the VD rats, which may be mediated by its reducing the neuronal apoptosis and modulating the expression of apoptosis-related protein Bcl-2 and bax.
展开▼
