摘要
目的 评价尼莫地平预先给药对老龄大鼠术后认知功能障碍的影响.方法 健康雄性SD大鼠90只,18月龄,体重400～500 g,采用随机数字表法分为3组（n=30）：尼莫地平对照组（N组）、手术组（S组）和尼莫地平＋手术组（N＋S组）.N组和N＋S组腹腔注射尼莫地平1 mg/kg、S组腹腔注射等容量生理盐水30 min后,N组大鼠吸入纯氧2h,S组和N＋S组大鼠吸入1.8％异氟醚麻醉下行脾脏切除术.于术前1d、术后1、3和7d时行Morris水迷宫实验;并于术前1d、术后1和7d时Morris水迷宫实验结束后随机取10只大鼠处死,取海马组织,采用流式细胞术测定海马神经元凋亡率、胞浆Ca2＋浓度（[Ca2＋]i）;采用RT-PCR法检测海马Bcl-2、Bax的mRNA表达;透射电镜下观察大鼠海马神经元超微结构.结果 与术前1d时比较,S组和N＋S组术后各时点逃避潜伏期延长,原平台穿越次数减少,海马神经元凋亡率、[Ca2＋]i升高,Bcl-2 mRNA表达下调,Bax mRNA表达上调,Bax/Bcl-2 mRNA比值升高（P＜0.05）,N组给药后各时点逃避潜伏期、原平台穿越次数、海马神经元凋亡率、[Ca2＋]i、Bcl-2和Bax的mRNA表达差异无统计学意义（P＞0.05）;与S组比较,N＋S组术后逃避潜伏期缩短和原平台穿越次数增多,海马神经元凋亡率、胞浆[Ca2＋]i降低,Bcl-2 mRNA表达上调,BaxmRNA表达下调,Bax/Bcl-2 mRNA比值降低（P＜0.05）.S组和N＋S组海马神经元电镜下出现病理学损伤,S组损伤重于N＋S组.结论 尼莫地平预先给药可降低老龄大鼠术后认知功能障碍的发生,其机制可能与抑制钙超载引起的海马神经元凋亡有关.
Objective To evaluate the effect of preconditioning with nimodipine on postoperative cognitive dys function of aged rats, Methods Ninety healthy male Sprague-Dawley rats, aged 18 months, weighing 400-500 g, were randomly divided into 3 groups （ n = 30 each） using a random number table： nimodipine control group （group N）, surgery group （group S）, and nimodipine ＋ surgery group （N ＋ S group）. In N and N ＋ S groups, nimodipine 1 mg/kg was intraperitoneally injected, while the equal volume of normal saline was given instead in S group. 30 min later, group N inhaled pure oxygen for 2 h, and S and N ＋ S groups inhaled 1.8 % isoflourane for 2 h when splenectomy was performed. Morris water maze test was performed on 1 day before operation and 1st, 3rd and 7th days after operation. After the end of Morris water maze test at 1 day before operation and 1st and 7th days after operation, 10 rats were sacrificed and brains were removed and hippocampi were isolated for determination of apoptosis in hippocampal neurons, intracellular [ Ca2] i in cytoplasm, and hippocampal Bcl-2 and Bax mRNA expression and for examination of uhrastructure of hippocampal neurons. Results Compared with the value before administration, the escape latency was significantly prolonged, the frequency of crossing the original platform was decroased, apoptotic rate and [ Ca2＋] i were increased, Bcl-2 mRNA expression was down-regulated, and Bax mRNA expression and Bax/Bcl-2 mRNA ratio were up-regulated at each time point after operation in S and N ＋ S groups, and no significant changes were found in the parameters mentioned above in N group. Compared with group S, the escape latency was significantly shortened, the frequency of crossing the original platform was inecreased, apoptotic rate and [ Caz＋ ] i were decreased, Bcl-2 mRNA expression was up-regulated, and Bax mRNA expression was down-regulated at each time point after operation in group N ＋ S. Pathological changes were found in S and N ＋ S grcups and the damage wa
出处
《中华麻醉学杂志》
CAS
CSCD
北大核心
2014年第9期1054-1057,共4页
Chinese Journal of Anesthesiology
基金
河北省2012年度医学适用技术跟踪项目（GL2012046）
河北省科技支撑项目（14277750D）
关键词
尼莫地平
手术后并发症
老年人
认知障碍
Nimodipine
Postoperative complications
Aged
Cognition disorders
