右美托咪定预先给药对七氟烷麻醉下发育期大鼠海马神经元自噬的影响  

Effect of dexmedetomidine pretreatment on autophagy of hippocampal neurons in developing rats under sevoflurane anesthesia

作　　者：徐桂萍[1] 李茵 瞿莉[1] 阿里木江·司马义 Xu Guiping;Li Yin;Qu Li;Ali Mujiang·Simayi(Department of Anesthesiology,People′s Hospital of Xinjiang Uygur Autonomous Region Xinjiang Clinical Research Center for Anesthesia Management,Urumqi 830000,China;Graduate School of Xinjiang Medical University,Urumqi 830000,China)

机构地区：[1]新疆维吾尔自治区人民医院麻醉科,新疆麻醉管理临床医学研究中心,乌鲁木齐830000 [2]新疆医科大学研究生学院,乌鲁木齐830000

出　　处：《中华麻醉学杂志》2022年第5期556-559,共4页Chinese Journal of Anesthesiology

基　　金：新疆维吾尔自治区自然科学基金(2022D01C143)。

摘　　要：目的评价右美托咪定预先给药对七氟烷麻醉下发育期大鼠海马神经元自噬的影响。方法清洁级健康SD大鼠36只,雌雄不限,7日龄,体重12~15 g。采用随机数字表法分为3组(n=12):对照组(C组)、七氟烷组(S组)和七氟烷+右美托咪定组(S+D组)。出生第7~9天S+D组每天腹腔注射右美托咪定25μg/kg后行3%七氟烷暴露(吸入氧浓度29%,氧流量2 L/min,2 h/d);S组腹腔注射等体积生理盐水后行七氟烷暴露;C组腹腔注射等体积生理盐水后行混合气体暴露。于大鼠出生20 d时开始Morris水迷宫训练,进行定位航行实验和空间探索实验。水迷宫实验结束后,麻醉大鼠处死后取海马,采用Western blot法检测自噬微管相关蛋白轻链3抗体(LC3)、BECN1和P62的表达。结果与C组相比,S组和S+D组逃避潜伏期延长,穿越原平台位置次数减少,海马LC3和BECN1表达上调,P62表达下调(P<0.05);与S组相比,S+D组逃避潜伏期缩短,穿越原平台位置次数增加,海马LC3和BECN1表达下调,P62表达上调(P<0.05)。结论右美托咪定预先给药改善七氟烷致发育期大鼠认知功能障碍的机制与减少海马神经元过度自噬有关。Objective To evaluate the effect of dexmedetomidine pretreatment on the autophagy of hippocampal neurons in the developing rats under sevoflurane anesthesia.Methods Thirty-six clean-grade healthy Sprague-Dawley rats of either sex,aged 7 days,weighing 12-15 g,were divided into 3 groups(n=12 each)using a random number table method:control group(group C),sevoflurane group(group S),and sevoflurane plus dexmedetomidine group(group S+D).On 7-9 days after birth,and the animals were exposed to 3%sevoflurane(oxygen concentration inhaled 29%,oxygen flow 2 L/min,2 h/day)after intraperitoneal injection of 25μg/kg dexmedetomidine every day in group S+D,the animals were exposed to sevoflurane after intraperitoneal injection of the equal volume of normal saline in group S,and the animals were exposed to gas mixture after intraperitoneal injection of the equal volume of normal saline in group C.The Morris water maze test was carried out at 20 days after birth,and the place navigation test and spatial probe test were performed.After the end of Morris water maze test,the anesthetized rats were sacrificed,and the hippocampus was obtained for determination of the expression of microtubule-associated protein light chain 3(LC3),BECN1 and P62 by Western blot.Results Compared with group C,the escape latency was significantly prolonged,the frequency of crossing the original platform was decreased,the expression of LC3 and BECN1 was up-regulated,and the expression of P62 was down-regulated in group S and group S+D(P<0.05).Compared with group S,the escape latency was significantly shortened,the frequency of crossing the original platform was increased,the expression of LC3 and BECN1 was down-regulated,and the expression of P62 was up-regulated in group S+D(P<0.05).Conclusions The mechanism by which dexmedetomidine pretreatment improves sevoflurane-induced cognitive dysfunction is related to reduction of excessive autophagy in hippocampal neurons of developing rats.

关 键 词：右美托咪啶 麻醉药 吸入 海马 神经元 自噬 

分 类 号：R614[医药卫生—麻醉学]