摘要
目的探讨老龄大鼠术后认知功能障碍时自噬与凋亡的关系。方法健康雄性CD大鼠120只，18月龄，体重500-550g，采用随机数字表法分为4组（n=30）：对照组（C组）、手术组（S组）、自噬抑制剂3．甲基腺苷组（MA组）和自噬激动剂雷帕霉素组（R组）。MA组尾静脉注射自噬抑制剂3-甲基腺苷1mg／kg，R组尾静脉注射自噬激动剂雷帕霉素2mg／kg，S组尾静脉注射等容量生理盐水；30min后，S组、MA和R组在3％七氟醚麻醉下行剖腹探查术。分别于术前1d、术后3和7d时，每组取10只大鼠，行Morris水迷宫实验检测认知功能，然后处死，取海马组织，采用流式细胞术检测神经元凋亡率，采用Westernblot法检测微管相关蛋白1轻链3Ⅱ（LC3U）及Beclin-1的表达。结果与C组比较，S组、MA组和R组术后3和7d时逃避潜伏期延长，穿越原平台次数减少，海马神经元凋亡率升高，LC3Ⅱ和Beclin-1表达下调（P〈0．05）。与S组比较，MA组术后3和7d时逃避潜伏期延长，穿越原平台次数减少，海马神经元凋亡率升高，LC3Ⅱ和Beclin-1表达下调，R组术后3和7d时逃避潜伏期缩短，穿越原平台次数增加，海马神经元凋亡率下降，LC3Ⅱ和Beclin-1表达上调（P〈0．05）。结论老龄大鼠术后认知功能障碍的发生机制与抑制海马神经元自噬．促进其凋亡有关。
Objective To evaluate the relationship between autophagy and apoptosis during postop-erative cognitive dysfunction in aged rats. Methods One hundred and twenty healthy male Sprague-Dawley rats, aged 18 months, weighing 500-550 g, were divided into 4 groups （n= 30 each） using a random number table ： control group (group C) , surgery group (group S） , autophagy inhibitor 3-methyladenine group （group MA） and autophagy agonist rapamycin group （group R）. Autophagy inhibitor 3-methvlade-nine 1 mg/kg and autophagy agonist rapamycin 2 mg/kg were injected via the caudal vein in MA and R groups, respectively, while the equal volume of normal saline was given instead in group S. Exploratory laparotomy was performed under anesthesia with 3% sevoflurane 30 min later in S, MA and R groups. Ten rats of each group were selected on 1 day before operation and 3 and 7 days after operation, and Morris wa-ter maze test was performed to assess cognitive function. Then the rats were sacrificed, brains were removed and hippocampal tissues were obtained for detection of apoptosis in hippocampal neurons and the expression of microtubule-associated protein 1 light chain 3 11 (LC3 11) and Beelin-1 by Western blot. The apoptotic rate was calculated. Results Compared with group C, the escape latency was significantly prolonged, the frequency of crossing the original platform was decreased, the apoptotic rate was increased, and the expres-sion of LC3 II and Becfin-1 was down-regulated on 3 and 7 days after operation in S, MA and R groups （P〈0. 05）. Compared with group S, the escape latency was significantly prolonged, the frequency of crossing the original platform was decreased, the apoptotic rate was increased, and the expression of LC3 Ⅱ and Beclin-1 was down-regulated in group MA, and the escape latency was significantly shortened, the fre-quency of crossing the original platform was increased, the apoptotic rate was decreased, and the expres-sion of LC3 Ⅱ and Beclin-1 was up-regulated in group R （P〈O. 05）.
作者
张琦
袁天宝
杨淑红
李亚南
王秀丽
王秋筠
Zhang Oi;Yuan Tianbao;Yang Shuhong;Li Yanan;Wang Xiuli;Wang Oiujan(Department of Anesthesiology＇, Third Hospital of Hebei Medical University, Shifiazhuang 050051, China;Department of Anesthesiology, Hebei Eye Hospital, Xingtai 053000, Chin;Department of Second Operating Room, Third Hosptial of Hebei Medical Uni- versity, Shijiazhuang 050051, Chin)
出处
《中华麻醉学杂志》
CAS
CSCD
北大核心
2018年第2期159-162,共4页
Chinese Journal of Anesthesiology
基金
国家自然科学基金面上项目（81771134）
河北省自然科学基金面上项目（H2018206305）
河北省政府资助临床优秀人才培养和基础课题研究项目（361005）
关键词
认知障碍
老年人
自噬
细胞凋亡
海马
Cognition disorders
Aged
Autophagy
Apoptosis
Hippocampus
