氯沙坦对血管性痴呆大鼠认知功能的改善及胆碱能系统活性的影响简

目的研究氯沙坦对血管性痴呆（VaD）大鼠认知功能的改善和胆碱能系统活性的影响。方法将40只雄性SD大鼠随机分成四组：假手术组，模型组，氯沙坦低剂量[2mg／（kg·d）】组，氯沙坦高剂量[5mg／（kg·d）】组，每组10只。用双侧颈总动脉永久性结扎法（2VO）制备VaD大鼠模型，造模前予灌胃治疗，Morris水迷宫测试治疗后VaD大鼠认知功能的改善情况．Tunel染色测定各组大鼠海马脑组织内细胞凋亡的变化。免疫组织化学方法检测Bel—2、Bax蛋白表达，并测定乙酰胆碱转移酶（CHAT）活性。结果方差分析表明，潜伏期和跨越次数F值分别为33．23和25．20。氯沙坦灌胃治疗的VaD大鼠，与未予治疗的VaD大鼠组相比，治疗组大鼠找到平台的潜伏期缩短（P〈0．01），穿越平台次数增多（P〈0．01）；氯沙坦高剂量组较氯沙坦低剂量组逃避潜伏期时间减少，穿越平台次数增多（P〈0．01）。方差分析表明，凋亡细胞、Bcl-2蛋白及Bax蛋白F值分别为155．58、215．79和428．95。与模型组相比，氯沙坦治疗组大鼠脑组织海马区凋亡细胞数明显减少，抗凋亡基因Bcl-2蛋白表达显著增加，凋亡基因Bax蛋白表达降低，差异有高度统计学意义（P〈0．01）；氯沙坦高剂量组与氯沙坦低剂量组相比，Bcl-2蛋白表达增加，Bax蛋白表达下降，差异有高度统计学意义（P〈0．01）。方差分析表明，各组大鼠ChAT活力，值为13．61。氯沙坦治疗组脑组织ChAT活力明显升高，差异有高度统计学意义（P〈0．01）；氯沙坦高剂量组与氯沙坦低剂量组相比，脑组织ChAT活力显著升高，差异有高度统计学意义（P〈0．01）。结论氯沙坦治疗可以明显改善VaD大鼠的认知功能．其机制与调节凋亡相关蛋白的表达、促进乙酰胆碱的合成相关。

Influence of Losartan on cognitive function improvement and cholinergic neuron of rats with vascular dementia

Objective To study improvement of cognitive function impairment of vascular dementia （VaD） rats induced by a permanent bilateral ligation of common carotid arteries （2VO） after administration of Losartan. Methods 40 male SD rats were randomly divided into 4 groups： .sham-operation group, model group, low dose [2 mg/（kg.d）] of Losartan group, high dose [5 mg/（kg-d）] of Losartan group, the VaD rats models were established by 2VO. Pre-treatment VaD model was established by gavage of Losartan. Morris water test was performed to detect the improvement of cognitive function of VaD rats after treatment. Tunel staining was performed to detect the changes of cell apoptosis of hippocam- pus brain tissue in rats of all groups. Immunohistochemistry was performed to detect the expression of Bcl-2 protein and Bax protein, and the ChAT activity. Results Variance analysis showed that, the F value of incubation period and crossing times was 33.23 and 25.20 respectively. Compared with untreated VaD group, the incubation period of finding platform was shortened in treatment VaD group （P 〈 0.01）, and crossinz times increased （P 〈 0.01）. Compared with low dose of Losartan group, the incubation period of finding platform was shortened in high dose of Losartan group, and crossing times increased （P 〈 0.01）. Variance analy- sis showed that, the F value of apoptotie cell, Bcl-2 pro- tein and Bax protein was 155.58, 215.79 and 428.95 respectively. Compared with model group, in the Losartan treatment groups, the number of apoptotic cell of hippocampus brain tissue in rats reduced significantly, the expression of Bcl-2 protein increased significantly, the expression of Bax protein decreased significantly, the differences were statistically significant （P 〈 0.01）. Compared with low dose of Losartan group, the expression of Bcl-2 protein increased and the expression of Bax protein was decreased in high dose of Losartan group, the differences were statistically significant （P 〈 0.01）. Variance analysis showed that, the F value of ChAT activity in all groups was 13.61. The ChAT activities of Losartan treatment groups increased, the differences were statistically significant （P 〈 0.01）. Compared with low dose of Losartan group, the ChAT activity of high dose of Losar- tan group increased, the difference was statistically significant （P 〈 0.01）. Conclusion Cognitive function impairment can be improved by administration of Losartan in VaD rats, which may be mediated by modulating the expression of apoptosis-related protein and promoting acetylcholine synthesis.