右美托咪定对脑缺血再灌注大鼠海马BDNF/TrκB信号通路的影响  

Effect of dexmedetomidine on hippocampal BDNF/TrκB signaling pathway in a rat model of cerebral ischemia-reperfusion injury

作　　者：阿里木江·司马义 瞿莉[2] 赵萱 徐桂萍[2] Alimujiang Simayi;Qu Li;Zhao Xuan;Xu Guiping(Graduate School,Xinjiang Medical University,Urumqi 830011,China;Department of Anesthesiology,People′s Hospital of Xinjiang Uygur Autonomous Region,Xinjiang Clinical Research Center for Anesthesia Management,Urumqi 830000,China)

机构地区：[1]新疆医科大学研究生学院,乌鲁木齐830011 [2]新疆维吾尔自治区人民医院麻醉手术中心,新疆麻醉管理临床医学研究中心,乌鲁木齐830000

出　　处：《中华麻醉学杂志》2024年第11期1381-1385,共5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对脑缺血再灌注大鼠海马脑源性神经营养因子(BDNF)/酪氨酸激酶受体B(TrκB)信号通路的影响。方法清洁级健康SD大鼠45只,雌雄各半,5~6月龄,体质量200~250 g。采用随机数字表法将大鼠分为3组(n=15):假手术组(S组)、脑缺血再灌注组(I/R组)和右美托咪定+I/R组(Dex组)。采用阻塞大脑中动脉90 min恢复灌注的方法制备大鼠脑缺血再灌注损伤模型。Dex组缺血前30 min腹腔注射右美托咪定50μg/kg,S组和I/R组腹腔注射等容量生理盐水。于再灌注12 h时行神经功能缺陷评分,随后麻醉大鼠处死取海马,采用TTC法确定脑梗死体积百分比,TUNEL法观察海马神经细胞凋亡情况,Western blot法检测BDNF和TrκB表达,RT-PCR法检测BDNF mRNA和TrκB mRNA表达。结果与S组比较,I/R组和Dex组神经功能缺陷评分和脑梗死体积百分比升高,海马神经细胞凋亡数增多,BDNF和TrκB及其mRNA表达下调(P<0.05);与I/R组比较,Dex组神经功能缺陷评分和脑梗死体积百分比降低,海马神经细胞凋亡数减少,BDNF和TrκB及其mRNA表达上调(P<0.05)。结论右美托咪定减轻大鼠脑缺血再灌注损伤的机制可能与激活海马BDNF/TrκB信号通路有关。Objective To evaluate the effect of dexmedetomidine on the hippocampal brain-derived neurotrophic factor(BDNF)/tyrosine kinase receptor B(TrκB)signaling pathway in a rat model of cerebral ischemia-reperfusion(I/R).Methods Forty-five clean-grade healthy Sprague-Dawley rats,half male and half female,aged 5-6 months,weighing 200-250 g,were divided into 3 groups(n=15 each)using a random number table method:sham operation group(group S),cerebral I/R group(group I/R),and dexmedetomidine+I/R group(group Dex).A rat model of cerebral I/R injury was established by occluding the middle cerebral artery for 90 min followed by restoring perfusion.In group Dex,dexmedetomidine 50μg/kg was intraperitoneally injected at 30 min before ischemia,while the equal volume of normal saline was intraperitoneally injected in S and I/R groups.Neurological deficit scores were evaluated at 12 h of reperfusion.The rats were anesthetized and sacrificed,and the hippocampus was isolated for determination of the percentage of cerebral infarct size(by TTC method),expression of BDNF and TrκB(by Western blot),and expression of BDNF mRNA and TrκB mRNA(by real-time polymerase chain reaction)and for microscopic examination of cell apoptosis(by TUNEL method).Results Compared with group S,the neurological deficit scores and percentage of cerebral infarct size were significantly increased,the number of apoptotic hippocampal neurons was increased,and the expression of BDNF and TrκB protein and mRNA was down-regulated in I/R and Dex groups(P<0.05).Compared with group I/R,the neurological deficit scores and percentage of cerebral infarct size were significantly decreased,the number of apoptotic hippocampal neurons was reduced,and the expression of BDNF and TrκB protein and mRNA was up-regulated in group Dex(P<0.05).Conclusions The mechanism by which dexmedetomidine alleviates cerebral I/R injury may be related to activating hippocampal BDNF/TrκB signaling pathways in rats.

关 键 词：右美托咪啶 脑 再灌注损伤 脑源性神经营养因子 受体蛋白质酪氨酸激酶类 

分 类 号：R614[医药卫生—麻醉学]