摘要
目的 评价海马高迁移率族蛋白1（HMGB1）/晚期糖基化终末产物受体（RAGE）信号通路在老龄大鼠术后认知功能障碍中的作用.方法 健康雄性SD大鼠63只,18月龄,体重500～600 g,采用随机数字表法分为3组（n=21）：对照组（C组）、脾切除术组（S组）和HMGB1抑制剂丙酮酸乙酯组（EP组）.EP组于脾切除术后30 min时腹腔注射丙酮酸乙酯40 mg/kg,S组腹腔注射等容量不含丙酮酸乙酯溶液.于术前、术后1、3和7d时行Morris水迷宫实验测试认知功能,记录逃避潜伏期和靶象限活动时间比率.分别于术后1、3和7d水迷宫测试结束后,处死7只大鼠,取海马组织,采用Western blot法测定HMGB1和RAGE的表达,采用RT-PCR法测定HMGB1和RAGE的mRNA表达.结果 与C组比较,S组和EP组术后1和3d时逃避潜伏期延长,靶象限活动时间比率降低,海马HMGB1和RAGE及其mRNA表达上调（P＜0.05）;与S组比较,EP组术后1和3d时逃避潜伏期缩短,靶象限活动时间比率升高,海马HMGB1和RAGE及其mRNA表达下调（P＜0.05）.结论 海马HMGB1/RAGE信号通路的激活参与了老龄大鼠术后认知功能障碍的发生.
Objective To evaluate the role of hippocampal high-mobility group box 1 protein （HMGB1）/receptor for advanced glycation end products （RAGE） signaling pathway in postoperative cognitive dysfunction in aged rats.Methods Sixty-three healthy male Sprague-Dawley rats,aged 18 months,weighing 500-600 g,were randomly divided into 3 groups （n=21 each） using a random number table：control group （group C）,splenectomy group （group S） and HMGB1 inhibitor ethyl pyruvate group （group EP）.Ethyl pyruvate 40 mg/kg was injected intraperitoneally at 30 min after splenectomy in group EP,and the equal volume of solution without ethyl pyruvate was given in group S.Before operation and on days 1,3 and 7 after operation,Morris water maze test was performed to assess the cognitive function,and the escape latency and ratio of time spent in the target quadrant were recorded.After completion of Morris water maze test on days 1,3 and 7 after operation,7 rats were sacrificed,and hippocampal tissues were obtained for determination of the expression of HMGB1 and RAGE （by Western blot） and HMGB1 and RAGE mRNA （by real-time polymerase chain reaction）.Results Compared with group C,the escape latency was significantly prolonged,the ratio of time spent in the target quadrant was significantly decreased,and the expression of HMGB1 and RAGE protein and mRNA was significantly up-regulated on days 1 and 3 after operation in S and EP groups （P〈0.05）.Compared with group S,the escape latency was significantly shortened,the ratio of time spent in the target quadrant was significantly prolonged,and the expression of HMGB1 and RAGE protein and mRNA was significantly down-regulated on days 1 and 3 after operation in group EP （P〈0.05）.Conclusion Activation of hippocampal HMGB1/RAGE signaling pathway is involved in the development of postoperative cognitive dysfunction in aged rats.
出处
《中华麻醉学杂志》
CAS
CSCD
北大核心
2016年第8期938-941,共4页
Chinese Journal of Anesthesiology
基金
青岛市市南区科技局立项课题（2014-14-032-YY）
关键词
高迁移率族蛋白质类
晚期糖基化终末产物受体
海马
认知障碍
手术后并发症
老年人
High mobility group proteins
Advanced glycation end product-specific receptor
Hippocampus
Cognition disorders
Postoperative complications
Aged
