海马AMPK信号通路在星状神经节阻滞减轻老龄大鼠术后认知功能障碍中的作用

Role of hippocampal AMPK signaling pathway in reduction of postoperative cognitive dysfunction by stellate ganglion block in aged rats

目的 评价海马单磷酸腺苷激活蛋白激酶（AMPK）信号通路在星状神经节阻滞减轻老龄大鼠术后认知功能障碍中的作用.方法 健康雄性老龄SD大鼠120只,18～22月龄,体重450～550 g,采用随机数字表法分为5组（n=24）：假手术组（S组）、术后认知功能障碍组（POCD组）、星状神经节阻滞组（SGB组）、星状神经节阻滞＋AMPK抑制剂组（SI组）和AMPK抑制剂组（AI组）.SGB组和SI组注射0.25％布比卡因0.15 ml行右侧星状神经节阻滞,给药结束后15 min实施手术.SI组和AI组手术结束时腹腔注射AMPK抑制剂Compound C 20 mg/kg.于术前1d、术后1、3和5d时进行Morris水迷宫实验,记录大鼠逃避潜伏期和游泳路径;随后处死大鼠取海马,采用Western blot法测定AMPK及磷酸化AMPK（p-AMPK）的表达.结果 与S组比较,POCD组、SI组和AI组大鼠逃避潜伏期和游泳路径延长,海马AMPK和p-AMPK表达下调（P＜0.05）;与POCD组比较,SGB组大鼠逃避潜伏期和游泳路径缩短,海马AMPK和p-AMPK表达上调（P＜0.05）;与SGB组比较,SI组和AI组大鼠逃避潜伏期和游泳路径延长,海马AMPK和p-AMPK表达下调（P＜0.05）.结论 海马AMPK信号通路激活参与了星状神经节阻滞减轻老龄大鼠术后认知功能障碍的过程.

Objective To evaluate the role of hippocampal AMP-activated protein kinase （AMPK） signaling pathway in reduction of postoperative cognitive dysfunction （POCD） by stellate ganglion block （SGB） in aged rats.Methods One hundred and twenty male Sprague-Dawley rats, aged 18-22 months, weighing 450-550 g, were randomly divided into 5 groups （n=24 each） using a random number table： sham operation group （group S）;group POCD;group SGB;SGB ＋ AMPK inhibitor group （group SI）;AMPK inhibitor group （group AI）.SGB was performed with 0.25% bupivacaine 0.15 ml in POCD, SGB and SI groups.Operation was performed at 15 min after the end of administration.Compound C （AMPK inhibitor） 20 mg/kg was injected intraperitoneally at the end of surgery in groups SI and AI.Morris water maze test was performed at 1 day before operation and on 1, 3 and 5 days after operation.The escape latency and swimming distance were recorded.The rats were then sacrificed, and the brains were removed for determination of the expression of AMPK and phosphorylated AMPK （p-AMPK） by Western blot.Results Compared with group S, the escape latency and swimming distance were significantly prolonged, and the expression of AMPK and p-AMPK was down-regulated in POCD, SI and AI groups.Compared with group POCD, the escape latency and swimming distance were significantly shortened, and the expression of AMPK and p-AMPK was up-regulated in group SGB.Compared with group SGB, the escape latency and swimming distance were significantly prolonged, and the expression of AMPK and p-AMPK was down-regulated in SI and AI groups.Conclusion Activation of hippocampal AMPK signaling pathway is involved in SGB-induced reduction of POCD in aged rats.