抑制环氧合酶⁃2表达对大鼠脑缺血/再灌注损伤后神经元凋亡的影响  

Effect of inhibiting cyclooxygenase⁃2 expression on neuronal apoptosis after cerebral ischemia/re⁃perfusion injury in rats

作　　者：杨迎春[1] 杨莹 张小良[1] 高赛红[1] 姜庆良 李宇凤 YANG Ying-chun;YANG Ying;ZHANG Xiao-liang;GAO Sai-hong;JIANG Qing-liang;LI Yu-feng(Department of Anatomy,Fenyang College of Shanxi Medical University,Shanxi Fenyang 032200,China)

机构地区：[1]山西医科大学汾阳学院解剖学教研室,山西汾阳032200

出　　处：《解剖学报》2024年第6期693-698,共6页Acta Anatomica Sinica

基　　金：山西医科大学汾阳学院科技扶持基金(2019C02);吕梁市社会发展领域重点研发项目(2022SHFZ24);山西省高等学校科技创新项目(2022L674)。

摘　　要：目的探讨大鼠脑缺血/再灌注(CI/R)损伤后环氧合酶-2(COX-2)引起神经元凋亡的作用机制。方法45只雄性SD大鼠,随机数字法分为3组:假手术组(sham)、模型组(CI/R)和COX-2抑制剂组(NS-398)。阻塞大脑中动脉建立模型,缺血开始时,NS-398组经腹腔注射NS-398(20 mg/kg),假手术组和模型组注射等量的DMSO。缺血2 h时对大鼠进行神经功能学评分,再灌注24 h时,2,3,5-氯化三苯四氮唑(TTC)染色检测大鼠脑梗死体积,同时取缺血侧额顶叶皮质半暗带区脑组织,Nissl染色检测神经元的损伤,TUNEL法检测神经元的凋亡,Western blotting检测COX-2、Bax和Bcl-2蛋白的表达水平。结果CI/R组大鼠神经功能学评分、脑梗死灶体积、凋亡指数、COX-2和Bax蛋白表达水平均高于假手术组(P<0.05),而Bcl-2蛋白表达水平和神经元数目均低于假手术组(P<0.05);NS-398组大鼠神经功能学评分、脑梗死灶体积、凋亡指数、COX-2和Bax蛋白表达水平均低于CI/R组(P<0.05),同时,Bcl-2蛋白表达水平和神经元数目均高于CI/R组(P<0.05)。结论COX-2可能通过调控Bcl-2和Bax的表达促进脑缺血/再灌注损伤后神经元的凋亡。Objective To investigate the mechanism of neuronal apoptosis induced by cyclooxygenase⁃2(COX⁃2)after cerebral ischemia/reperfusion(CI/R)injury in rats.Methods Totally 45 male SD rats were divided into 3 groups by random number method,sham operation group(sham),model group(CI/R),COX⁃2 inhibitor group(NS⁃398).Blocking the middle cerebral artery to create a model,at the beginning of ischemia,NS⁃398 group was intraperitoneally injected with NS⁃398(20 mg/kg),while sham group and CI/R group were injected with the same amount of DMSO.Rats were performed for neurofunctional scores after 2 hours ischemia.After 24 hours reperfusion,2,3,5⁃triphenyltetrazolium chloride(TTC)staining was used to detect the infarct volume of rats.Meanwhile,cerebral tissue from penumbra area of frontal parietal cortex on ischemic side was taken,Nissl staining and TUNEL method were used to detect neuronal damage and apoptosis respectively,and finally Western blotting was used to detect the expression levels of COX⁃2,Bcl⁃2 and Bax proteins.Results The neurofunctional scores of rats,cerebral infarction volume,apoptosis index,the expressions of COX⁃2 and Bax in CI/R group were higher than those in the sham group(P<0.05),the expression level of Bcl⁃2 and the number of neurons were lower than those in the sham group(P<0.05);The neurofunctional scores of rats,cerebral infarction volume,apoptosis index,the expression levels of COX⁃2 and Bax in NS⁃398 group were lower than those in CI/R group(P<0.05),the expression level of Bcl⁃2 and the number of neurons were higher than those in CI/R group(P<0.05).Conclusion COX⁃2 may promote neuronal apoptosis after cerebral ischemia/reperfusion injury by regulating the expressions of Bcl⁃2 and Bax.

关 键 词：环氧合酶-2 脑缺血再灌注损伤 神经元 免疫印迹法 大鼠 

分 类 号：R322.8[医药卫生—人体解剖和组织胚胎学]