萝卜硫素对心肌缺血再灌注损伤大鼠IRE-1/XBP-1通路及心肌凋亡的影响  

Influence of sulforaphane on IRE-1/XBP-1 pathway and myocardial apoptosis in rats with myocardial ischemia reperfusion injury

作　　者：王帅 邢彩耐 邬鹏宇 崔志成 赵长全 Wang Shuai;Xing Cainai;Wu Pengyu;Cui Zhicheng;Zhao Changquan(Department of Cardiovascular Surgery,Affiliated Hospital of North China University of Science and Technology,Tangshan 063000,China;不详)

机构地区：[1]华北理工大学附属医院心脏血管外科,唐山063000 [2]华北理工大学附属医院心内科,唐山2063000

出　　处：《中国循证心血管医学杂志》2021年第11期1331-1335,共5页Chinese Journal of Evidence-Based Cardiovascular Medicine

基　　金：河北省中医药管理局科研计划项目(2018184)。

摘　　要：目的探究萝卜硫素(SFN)对心肌缺血再灌注损伤(MIRI)大鼠心肌凋亡及肌醇需求酶1(IRE-1)/X-盒结合蛋白-1(XBP-1)通路的影响。方法实验分为假手术组、模型组、SFN组、STF-083010组、SFN+STF-083010组五组,每组10只。冠状动脉左室支结扎前2 h,SFN组尾静脉注射5 mg/kg SFN,STF-083010组腹腔注射30 mg/kg STF-083010,SFN+STF-083010组在SFN组基础上腹腔注射30 mg/kg STF-083010,假手术组、模型组尾静脉和腹腔注射等体积生理盐水。除假手术组外,其余各组冠状动脉左室支结扎大鼠,假手术组仅打开胸腔暴露出心脏穿丝线而不结扎。TTC染色检测心肌梗死情况;苏木精-伊红(HE)染色观察大鼠心肌组织形态学情况;TUNEL染色观察心肌组织细胞凋亡情况;实时荧光定量PCR(qRT-PCR)检测心肌组织中半胱氨酸天冬氨酸蛋白酶3(caspase3)、B淋巴细胞瘤-2基因(BCL2)、Bcl-2相关X蛋白(BAX)mRNA表达;免疫印迹法检测心肌组织中IRE-1、p-IRE-1、XBP-1蛋白表达。结果模型组心肌细胞排列紊乱,细胞膜破坏严重,细胞核部分散落在外;SFN组心肌细胞排列紊乱部分缓解,见少量细胞核散落;STF-083010组心肌细胞排列紊乱,细胞核散落严重;SFN+STF-083010组细胞排列恢复正常,排列整齐。与假手术组比较,模型组心肌梗死体积百分比、心肌组织细胞凋亡率,caspase3、BAX mRNA水平,p-IRE-1/IRE-1、XBP-1蛋白水平升高(P<0.05),BCL2 mRNA水平降低(P<0.05);与模型组比较,SFN组、STF-083010组、SFN+STF-083010组心肌梗死体积百分比、心肌组织细胞凋亡率,caspase3、BAX mRNA水平,p-IRE-1/IRE-1、XBP-1蛋白水平降低(P<0.05),BCL2 mRNA水平升高(P<0.05);分别与SFN组、STF-083010组比较,SFN+STF-083010组心肌梗死体积百分比、心肌组织细胞凋亡率,BAX mRNA水平,p-IRE-1/IRE-1、XBP-1蛋白水平降低(P<0.05);与STF-083010组比较,SFN+STF-083010组caspase3 mRNA水平降低(P<0.05),BCL2 mRNA水平升高(P<0.05)。结论SFN通过抑制IRE-1/XBP-1通路缓解Objective To study the influence of sulforaphane(SFN) on inositol-requiring enzyme 1/X-box binding protein-1(IRE-1/XBP-1) pathway and myocardial apoptosis in rats with myocardial ischemia reperfusion injury(MIRI). Methods All rats were divided into sham-operation group, model group, SFN group, STF-083010 group and SFN+STF-083010 group(each n=10). The situation of myocardial infarction was detected by using TTC staining, myocardial histomorphology was observed through HE staining, and myocardial apoptosis was observed by using TUNEL staining. The mRNA expressions of cystein-asparate protease 3(caspase3), B-cell lymphoma-2(BCL2),and Bcl-2 associated X protein(BAX) were detected by using qRT-PCR. The protein expressions of IRE-1, p-IRE-1 and XBP-1 were detected by using Western blotting assay. Results The disordered arrangement of cardiomyocytes,serious destroyed cell membrane and partly scattered nucleus were observed in model group. The disordered arrangement of cardiomyocytes and a little scattered nucleus were observed in SFN group. The disordered arrangement of cardiomyocytes and serious scattered nucleus were observed in STF-083010 group. The normal and aligned arrangement of cardiomyocytes was observed in SFN+STF-083010 group. Compared with sham-operation group,the percentage of myocardial infarction volume, apoptosis rate of cardiomyocytes, caspase3 and BAX mRNA levels,p-IRE-1/IRE-1 and XBP-1 protein levels increased(P<0.05), and BCL2 mRNA level decreased(P<0.05) in model group. Compared with model group, the percentage of myocardial infarction volume, apoptosis rate of cardiomyocytes,caspase3 and BAX mRNA levels, p-IRE-1/IRE-1 and XBP-1 protein levels decreased(P<0.05), and BCL2 mRNA level increased(P<0.05) in SFN group, STF-083010 group and SFN+STF-083010 group. Compared with SFN group and STF-083010 group, the percentage of myocardial infarction volume, apoptosis rate of cardiomyocytes, BAX m RNA level, p-IRE-1/IRE-1 and XBP-1 protein levels decreased in SFN+STF-083010 group(P<0.05). Compared with STF-083

关 键 词：萝卜硫素 心肌缺血再灌注损伤 心肌凋亡 肌醇酶1/X-盒结合蛋白-1通路 大鼠 

分 类 号：R542.2[医药卫生—心血管疾病]