右美托咪定对心肌缺血再灌注所致脑损伤的影响  

Effects of dexmedetomidine on brain injury induced by myocardial ischemia reperfusion

作　　者：吴科帆 张爱宁 季烨龙 张艺[1] 江梦[1] 夏中元[1] Wu Kefan;Zhang Aining;Ji Yelong;Zhang Yi;Jiang Meng;Xia Zhongyuan(Dept of Anesthesiology,Renmin Hospital of Wuhan University,Wuhan 430060)

机构地区：[1]武汉大学人民医院麻醉科,武汉430060

出　　处：《安徽医科大学学报》2022年第2期265-268,共4页Acta Universitatis Medicinalis Anhui

基　　金：国家自然科学基金(编号:81801309)。

摘　　要：目的探讨右美托咪定对心肌缺血再灌注所致脑损伤中炎症因子及内质网应激的影响。方法SPF级健康雄性SD大鼠24只,体质量(200~220)g,(6~8)周龄,采用随机数字表法分为3组(n=8):假手术组(S组)、心肌缺血再灌注组(IR组)、心肌缺血再灌注+右美托咪定组(IR+Dex组)。大鼠适应饲养环境后,采用结扎左冠状动脉前降支30 min后再灌注120 min的方法建立心肌缺血再灌注损伤模型。于再灌注开始时给予IR+Dex组25μg/kg右美托咪定,S组和IR组注射等容量0.9%氯化钠溶液。断头处死大鼠取脑组织,光镜下观察大鼠海马HE染色的细胞结构变化。ELISA法检测血清炎性因子IL-6、IL-8、IL-10。Western blot法测定大鼠海马组织中CCAAT-增强子结合蛋白同源蛋白(Chop)、免疫球蛋白结合蛋白(Bip)、真核生物起始因子2(eif-2α)和蛋白激酶RNA样内质网激酶PERK(protein kinase RNA-like endoplasmic reticulum kinase,PERK)的表达水平。结果与S组比较,IR组和IR+Dex组脑组织病理损伤加重,血清炎性因子IL-6、IL-8表达增加(P<0.05),IL-10表达减少(P<0.05),海马组织中Chop、Bip、磷酸化真核生物起始因子2(p-eif-2α)和磷酸化蛋白激酶RNA样内质网激酶(p-perk)蛋白表达上调(P<0.05);与IR组比较,IR+Dex组脑组织病理损伤减轻,IL-6、IL-8表达下调(P<0.05),IL-10表达增加(P<0.05),海马组织中Chop、Bip、p-eif-2α和p-perk的表达下调(P<0.05)。结论右美托咪定预处理可减轻心肌缺血再灌注所致的脑损伤,其机制可能与抑制全身炎症反应和内质网应激有关。Objective To investigate the effects of dexmedetomidine on inflammatory factors and endoplasmic reticulum stress in myocardial ischemia reperfusion induced brain injury.Methods Twenty-four SPF-grade healthy male SD rats,weighing(200~220)g and aged(6~8)weeks,were divided into three groups(n=8)by random number table method:sham operation group(S group),myocardial ischemia reperfusion group(IR group)and myocardial ischemia/reperfusion+Dex group(IR+Dex group).After the rats were adapted to the feeding environment,the myocardial ischemia reperfusion injury model was established by ligating the anterior descending branch of the left coronary artery for 30 min and reperfusion for 120 min.At the beginning of reperfusion,IR+Dex group was given 25μg/kg dexmedetomidine,S group and IR group were injected with equal volume normal saline.Rats were sacrificed by decapitation and brain tissue was taken and the changes of hippocampal cell structure of rats stained by HE were observed under light microscope.Serum inflammatory factors IL-6,IL-8 and IL-10 were detected by ELISA.The expressions of Chop,Bip,p-eif-2αand p-perk in rat hippocampal tissues were determined by Western blot.Results Compared with the S group,the IR group and the IR+Dex group showed aggravation of brain lesions,increased expression of inflammatory cytokines IL-6 and IL-8(P<0.05),and decreased expression of IL-10(P<0.05).Hippocampal Chop,Bip,p-eif-2αand p-perk proteins were up-regulated(P<0.05).Compared with IR group,IR+Dex group showed reduced pathological injury,decreased expression of IL-6 and IL-8(P<0.05),increased expression of IL-10(P<0.05),and down-regulated expressions of Chop,Bip,p-eif-2αand p-perk in hippocampal tissues(P<0.05).Conclusion Dexmedetomidine preconditioning can reduce the brain injury caused by myocardial ischemia reperfusion,and its mechanism may be related to the inhibition of systemic inflammatory response and endoplasmic reticulum stress.

关 键 词：右美托咪定 脑损伤 心肌缺血再灌注 内质网应激 炎症因子 

分 类 号：R614.2[医药卫生—麻醉学]