中文摘要：

【摘要】目的评价尼莫地平对老龄大鼠海马钙调神经磷酸酶（CaN）活性的影响。方法健康雄性SD大鼠60只，18月龄，体重550～650g，采用随机数字表法分为2组（n=30）：手术组（S组）和尼莫地平组（N组）。N组腹腔注射尼莫地平1mg／kg，S组腹腔注射等容量生理盐水，30min后行剖腹探查术。分别于术前1d和术后3、7d时，每组随机取10只大鼠行Morris水迷宫实验。水迷宫实验结束后取大鼠海马组织，采用流式细胞术测定海马神经元凋亡率，采用Westernblot法测定CaN、磷酸化BAD（p-BAD）和caspase-3的表达水平。结果与术前1d时比较，S组术后各时点逃避潜伏期延长，穿越原平台次数减少，平台所在象限停留时间缩短，海马神经元凋亡率升高，海马组织CaN、p-BAD和caspase-3的表达上调（P〈0．05）；与S组比较，N组术后各时点逃避潜伏期缩短，穿越原平台次数增加，平台所在象限停留时间延长，海马神经元凋亡率降低，海马组织CaN、p-BAD和caspase-3的表达下调（P〈0．05）。结论尼莫地平抑制海马神经元凋亡，减轻老龄大鼠术后认知功能障碍的机制可能与抑制CaN的激活有关。

英文摘要：

Objective To evaluate the effect of nimodipine on the activity of calcineurin （CaN） in the hippocampus of aged rats. Methods Sixty healthy male Sprague-Dawley rats, aged 18 months, weighing 550-650 g, were divided into 2 groups （n= 30 each） using a random number table： surgery group （group S） and nimodipine group （group N）. Nimodipine 1 mg/kg was intraperitoneally injected in group N, while the equal volume of normal saline was given instead in group S, and 30 rain later explorato- ry laparotomy was performed. Ten rats in each group were randomly selected on 1 day before operation and 3 and 7 days after operation, and Morris water maze test was performed. After the end of Morris water maze test, 10 rats were selected and sacrificed, brains were removed, and hippocampi were isolated for detec- tion of apoptosis in hippocampal neurons （by flow cytometry） and expression of CaN, phosphor-BAD （p- BAD） and caspase-3 in hippocampal tissues （by Western blot）. Apoptotic rate was calculated. Results Compared with the value at 1 day before operation, the escape latency was significantly prolonged, the fre-queney of crossing the original platform was decreased, the time of staying at the platform quadrant was shortened, apuptotie rate was inereased, and the expression of CaN, p-BAD and easpase-3 in hippocampal tissues was up-regulated at eaeh time point after operation in group S （P〈0.05）. Compared with group S, the escape latency was significantly shortened, the frequency of crossing the original platform was in- creased, the time of staying at the platform quadrant was prolonged, apoptotic rate was decreased, and the expression of CaN, p-BAD anti easpase-3 in hippoeampal tissues was down-regulated at eaeh time point af- ter operation in group N （P〈0.05）. Conclusion The mechanism by which nimodipine inhibits apoptosis in hippoeampal neurons and reduees postoperative cognitive dysfunction may be related to inhibition of CaN aetivation in aged rats.