右美托咪定通过AMPK/mTOR通路对老年大鼠术后认知功能障碍的影响  

Effect of dexmedetomidine through AMPK/mTOR pathway on post-operative cognitive dysfunction in elderly rats

作　　者：张倩 张志卓 王欢 李瑞冰 ZHANG Qian;ZHANG Zhizhuo;WANG Huan;LI Ruibing(Department of Anesthesiology,Xingtai Third Hospital,Xingtai 054000,Hebei,China;Operation Room,Xingtai Third Hospital,Xingtai 054000,Hebei,China;Department of Cardiovascular Surgery,Xingtai Third Hospital,Xingtai 054000,Hebei,China)

机构地区：[1]河北省邢台市第三医院麻醉科,河北邢台054000 [2]河北省邢台市第三医院手术室,河北邢台054000 [3]河北省邢台市第三医院心外科,河北邢台054000

出　　处：《贵州医科大学学报》2022年第11期1300-1305,1331,共7页Journal of Guizhou Medical University

基　　金：河北省重点研发自筹项目(172777200);邢台市科学技术局基金项目(2019ZC202)。

摘　　要：目的探究盐酸右美托咪定通过腺苷酸激活蛋白激酶/雷帕霉素靶蛋白通路(AMPK/mTOR)对老年大鼠术后认知功能障碍(POCD)的改善作用。方法选取SPF级健康SD老年大鼠60只随机分为假手术组、模型组、右美托咪定低剂量组及右美托咪定高剂量组,每组15只,假手术组大鼠手术不切除肝叶,其余3组大鼠手术切除部分肝叶制作认知功能障碍模型;采用Zea-Longa评分法评估各组大鼠术后1、6、12、24、72 h时认知障碍情况,Western blot检测各组大鼠AMPK/mTOR通路相关蛋白AMPK、mTOR与凋亡相关蛋白B淋巴细胞瘤-2基因相关蛋白X(BAX)、半胱氨酸-天冬氨酸蛋白酶3(Caspase-3)等表达水平;Real-time PCR检测AMPK、mTOR、BAX、Caspase-3的mRNA水平,TUNEL染色观察各组海马组织结构,通过ELISA法检测海马组织炎症指标白细胞介素-1β(IL-1β)与肿瘤坏死因子-α(TNF-α)水平。结果术后1、6、12、24、72 h时,模型组、右美托咪定低剂量组、右美托咪定高剂量组Zea-Longa评分显著高于假手术组,低剂量组与高剂量组大鼠神经功能缺损评分显著低于模型组、且高剂量组评分略低于低剂量组,差异有统计学意义(P<0.05);右美托咪定组大鼠海马组织AMPK、mTOR、BAX与Caspase-3的蛋白水平高于假手术组,但明显低于模型组,差异有统计学意义(P<0.05),mRNA结果与蛋白结果较为一致;TUNEL病理染色结果显示,右美托咪定组大鼠海马CA1区神经元数量与模型组比较明显增加,神经元凋亡指数明显降低、且高剂量组凋亡情况低于低剂量组(P<0.05);ELISA结果显示,模型组术后海马组织IL-1β与TNF-α水平高于右美咪定组,而右美咪定低剂量组IL-1β与TNF-α水平高于高剂量组(P<0.05)。结论右美托咪定可改善老年大鼠术后认知障碍情况,减少海马组织神经元凋亡及炎症反应,其机制可能与调控凋亡相关信号通路AMPK/mTOR有关。Objective To investigate the ameliorative effect of dexmedetomidine hydrochloride on postoperative cognitive dysfunction(POCD)in aged rats through AMPK/mTOR pathway.Methods Sixty SPF SD rats were randomly divided into sham-operated group,model group,dexmedetomidine low-dose group and dexmedetomidine high-dose group,with 15 rats in each group.The liver lobes of the rats in the sham-operated group were remained,and the liver lobes of the rats in the rest 3 groups were resected to make the cognitive dysfunction model.The cognitive dysfunction conditions of each group at 1,6,12,24,and 72 hours after the surgery were evaluated by Zea-Longa;the expression levels of AMPK/mTOR pathway-related proteins(AMPK and mTOR)and apoptosis-related proteins(BAX and Caspase-3)were detected by Western blot;Real-time PCR was used to detect the expression levels of mRNA of AMPK,mTOR,BAX,and Caspase-3.The hippocampal tissue structure of each group was observed through TUNEL staining,and the inflammatory indexes(IL-1βand TNF-α)of hippocampal tissue were detected by ELISA.Results At 1,6,12,24 and 72 h after surgery,the Zea-Longa scores in the model group,dexmedetomidine low-dose group and dexmedetomidine high-dose group were significantly higher than those in the sham-operated group;the neurological deficit scores in the low-dose and high-dose groups were significantly lower than those in the model group,and the scores in the high-dose group were slightly lower than those in the low-dose group,with statistically significant differences(P<0.05);The protein levels of AMPK,mTOR,BAX,and Caspase-3 in hippocampal tissues of rats in the dexmedetomidine group were higher than those in the sham-operated group,but significantly lower than those in the model group,with statistically significant differences(P<0.05),and the mRNA results were consistent with the protein results;TUNEL pathological staining results showed that the number of neurons in the CA1 area of hippocampus of rats in the dexmedetomidine group significantly increased compared with

关 键 词：右美托咪定 AMPK/mTOR信号通路 术后认知功能障碍 凋亡 炎症 海马组织 

分 类 号：R966[医药卫生—药理学]