自噬在丙泊酚麻醉致老年大鼠术后认知功能障碍中的作用  

Role of autophagy in postoperative cognitive dysfunction of aged rats induced by propofol anesthesia

作　　者：杨宁[1] 李伦旭[1] 刘涛涛 韩登阳 李正迁[1] 倪诚[1] 徐懋[1] 郭向阳[1] YANG Ning;LI Lunxu;LIU Taotao;HAN Dengyang;LI Zhengqian;NI Cheng;GUO Xiangyang(Department of Anesthesiology, Peking University Third Hospital, Beijing 100191, China)

机构地区：[1]北京大学第三医院麻醉科,北京100191

出　　处：《药物评价研究》2018年第5期761-766,共6页Drug Evaluation Research

基　　金：国家自然科学基金资助项目(81571036);国家自然科学基金青年基金资助项目(81600933)

摘　　要：目的探讨丙泊酚麻醉对老年大鼠术后认知功能的影响及自噬在其中的作用。方法将老年大鼠72只,随机分为4组:对照组、丙泊酚组、雷帕霉素组、丙泊酚+雷帕霉素组。雷帕霉素组及丙泊酚+雷帕霉素组于麻醉前5 d ip雷帕霉素10mg/kg,每天1次,麻醉当日为麻醉前1 h注射,共6 d。丙泊酚组及丙泊酚+雷帕霉素组以20 mg/kg丙泊酚诱导麻醉,并以54 mg/kg/h维持4 h。采用Morris水迷宫评测大鼠学习与记忆功能;Western Blotting技术及免疫荧光观察麻醉后24 h、6 d海马区自噬相关蛋白的表达。结果与对照组比较,丙泊酚组第1~3天逃避潜伏期显著延长(P<0.05、0.01),目标象限探索时间明显缩短,穿平台次数明显减少(P<0.05);麻醉后24 h、6 d海马区自噬相关蛋白LC3B、Beclin-1蛋白表达明显减少,p62蛋白表达明显增多(P<0.05)。与丙泊酚组比较,丙泊酚+雷帕霉素组第1~3天逃避潜伏期缩短,目标象限探索时间显著延长,穿平台次数明显增加(P<0.05);麻醉后24 h、6 d海马区自噬相关蛋白LC3B、Beclin-1表达明显增多,p62表达明显减少(P<0.05)。结论丙泊酚连续麻醉4 h可导致老年大鼠空间学习记忆能力损伤,其机制可能与抑制海马区自噬有关。Objective To investigate the influence of propofol on learning and memory, and to identify the potential role of hippocampal autophagy in propofol-induced cognitive alterations in aged rats. Methods Tatolly 72 rats were randomly divided into four groups as follow： control group, propofol group（PRO）, rapamycin group（RAP）, and propofol ＋ rapamycin group（PRO＋RAP）. Rats in RAP and PRO＋RAP groups were ip injected with 10 mg/kg rapamycin beginning five days before propofol exposure. On the sixth day, rapamycin was administered 1 h before propofol anesthesia. Rats in both the PRO and PRO＋RAP groups received 20 mg/kg propofol to induce anesthesia and then 54 mg/kg/h propofol to maintain anesthesia for 4 h. The test of learning and memory was performed by Morris water maze. Autophagy-related proteins in hippocampal region were determined by Western blotting and immunofluorescent staining at 24 h and 6 d after anesthesia. Results Compared with the CON group, the escape latency significantly prolonged from 1-3 day, the probe time was significantly decreased, and the time of staying at the original platform quadrant was significantly shorter（P 〈 0.05 and 0.01） in the PRO group. Autophagy-related proteins LC3 B and Beclin-1 expression were significantly decreased and p62 expression was significantly increased（P 〈 0.05）. Compared with the PRO group, the escape latency significantly shortened from 1-3 day, the probe time was significantly increased, and the time of staying at the original platform quadrant was significantly longer in the PRO＋RAP group（P 〈 0.05）, and autophagy-related proteins LC3 B and Beclin-1 expression were significantly increased and p62 expression was significantly decreased（P 〈 0.05） in the PRO＋RAP group. Conclusions Our in vivo study indicates that 4 h propofol anesthesia could induce cognitive impairment in aged rats and this may be caused by the inhibitory effects of autophagy in the hippocampus.

关 键 词：自噬 丙泊酚 术后认知功能障碍 海马 老年大鼠 雷帕霉素 

分 类 号：R962.2[医药卫生—药理学]