右美托咪定后处理对大鼠脑缺血再灌注损伤及内质网应激的影响  

Effects of dexmedetomidine postconditioning on cerebral ischemia-reperfusion injury and endoplasmic reticulum stress in rats

作　　者：龙赤荣 王万初 吴胜男 于影[1] 高琴[3] 李正红[1] LONG Chi-rong;WANG Wan-chu;WU Sheng-nan;YU Ying;GAO Qin;LI Zheng-hong(Department of Physiology,Bengbu Medical College,Bengbu 233030,Anhui Province,China;School of Laboratory Medicine,Bengbu Medical College,Bengbu 233030,Anhui Province,China;Research Center,Bengbu Medical College,Bengbu 233030,Anhui Province,China)

机构地区：[1]蚌埠医学院生理教研室,安徽蚌埠233030 [2]蚌埠医学院检验医学院,安徽蚌埠233030 [3]蚌埠医学院科研中心,安徽蚌埠233030

出　　处：《中国临床药理学杂志》2023年第13期1908-1912,共5页The Chinese Journal of Clinical Pharmacology

基　　金：国家自然科学基金资助项目(81770297);安徽省自然科学基金资助项目(1508085MH170);蚌埠医学院大学生创新创业训练计划基金资助项目(bydc2021036)。

摘　　要：目的 探讨右美托咪定(Dex)后处理对大鼠脑缺血再灌注损伤(CIRI)及内质网应激(ERS)的影响。方法 将36只SD雄性大鼠随机分为假手术组、模型组和实验组,每组12只。模型组和实验组用线栓法进行缺血2 h再灌注24 h处理,构建大脑中动脉栓塞模型。实验组于再灌注30 min前腹腔注射100μg·kg^(-1) Dex,假手术组和模型组均腹腔注射等体积0.9%NaCl。用Longa评分法评估大鼠的神经功能缺损状况,用2,3,5-三苯基氯化四氮唑法检测大鼠脑梗死体积百分比,用酶联免疫吸附试验法检测大鼠海马组织中超氧化物歧化酶(SOD)和丙二醛(MDA)的含量,用蛋白质印迹法测定G蛋白偶联受体78(GRP78)、C/EBP同源蛋白(CHOP)和胱天蛋白酶12(caspase-12)的表达水平。结果 假手术组、模型组和实验组的神经功能缺损评分分别为0、(2.58±0.49)和(1.25±0.43)分,脑梗死体积比分别为0、(19.56±6.87)%和(10.01±6.58)%,SOD分别为(206.61±11.56)、(116.83±3.78)和(174.91±2.44)U·mg prot^(-1),MDA分别为(4.94±0.30)、(9.55±0.23)和(7.33±0.52)U·mg prot^(-1),GRP78蛋白相对表达水平分别为1.00±0.15、1.74±0.02和2.08±0.08,CHOP蛋白相对表达水平分别为1.00±0.31、2.82±0.14和1.84±0.15,caspase-12蛋白相对表达水平分别为1.00±0.35、2.42±0.09和1.60±0.26。模型组的上述指标与实验组和假手术组比较,差异均有统计学意义(P<0.05,P<0.01)。结论 Dex可通过上调GRP78、下调CHOP而影响脑缺血再灌注损伤大鼠的内质网应激反应,提高细胞活力,缩小脑梗死灶体积,抑制细胞凋亡,具有一定的脑保护作用。Objective To investigate the effects of dexmedetomidine(Dex)postconditioning on cerebral ischemia-reperfusion injury(CIRI)and endoplasmic reticulum stress(ERS)in rats.Methods Thirty six male SD rats were randomly divided into sham-operation group,model group and experimental group,with 12 rats per group.The model and experimental groups were treated with ischemia 2 h and reperfusion 24 h with thread embolism method to establish the middle cerebral artery occlusion model.Experimental group was injected with 100μg·kg^(-1)Dex intraperitoneally 30 min before reperfusion,sham-operation and model groups were given the same volume of 0.9%NaCl.Evaluation of neurological deficit in rats by Longa scoring method.The volume percentage of cerebral infarction was measured by 2,3,5-triphenyl tetrazolium chloride.The contents of superoxide dismutase(SOD)and malondialdehyde(MDA)in hippocampus of rats were detected by enzyme-linked immunosorbent assay.Western blot was used to detect the protein expression levels of endoplasmic reticulum stress proteins(GRP78),C/EBP homologous protein(CHOP)and caspase-12.Results The Longa scores of sham-operation,model and experimental groups were 0,(2.58±0.49)and(1.25±0.43)scores;the volume ratios of cerebral infarction were 0,(19.56±6.87)%and(10.01±6.58)%;SOD levels in the hippocampus were(206.61±11.56),(116.83±3.78)and(174.91±2.44)U·mg prot^(-1);MDA levels in the hippocampus were(4.94±0.30),(9.55±0.23)and(7.33±0.52)U·mg prot^(-1);the relative expression levels of GRP78 were1.00±0.15,1.74±0.02 and 2.08±0.08;the relative expression levels of CHOP were 1.00±0.31,2.82±0.14and 1.84±0.15;the relative expression levels of caspase-12 were 1.00±0.35,2.42±0.09 and 1.60±0.26.The differences of above indicators were statistically significant between the model group and sham-operation and experimental groups(P<0.05,P<0.01).Conclusion Dex can affect the endoplasmic reticulum stress response of rats with cerebral ischemia-reperfusion injury by up regulating GRP78 and down regulating CHOP

关 键 词：右美托咪定 脑缺血再灌注损伤 内质网应激 细胞凋亡 

分 类 号：R971.2[医药卫生—药品]