七氟烷介导miR-146a-5p/TRIP6轴调控线粒体凋亡改善心肌缺血再灌注心肌损伤  

Sevoflurane mediates miR-146a-5p/TRIP6-axis to regulate mitochondrial apoptosis and improve myocardial ischemia reperfusion injury

作　　者：张姗 秦文东 蒋淼[1] ZHANG Shan;QIN Wen-dong;JIANG Miao(Department of Anesthesiology,Renhe Hospital,Baoshan Branch,Huashan North Hospital,Fudan University,Shanghai 200942;Department of Anesthesiology,Shanghai Fourth People's Hospital,Shanghai 200081,China)

机构地区：[1]复旦大学附属华山北院宝山分院仁和医院麻醉科,上海200942 [2]上海第四人民医院麻醉科,上海200081

出　　处：《解剖科学进展》2022年第3期355-358,363,共5页Progress of Anatomical Sciences

基　　金：上海市宝山区科技创新专项资金项目(17-E-19)。

摘　　要：目的 探究七氟烷对心肌缺血再灌注大鼠心肌损伤的改善作用及可能机制。方法 SD大鼠随机分为假手术组(Sham组)、心肌缺血再灌注损伤组(IR组)和七氟烷组(Sev组),每组10只。HE染色检测大鼠心肌组织病理形态变化;TUNEL实验检测大鼠心肌组织细胞凋亡;Western blot检测心肌组织线粒体凋亡相关蛋白表达;qRT-PCR检测心肌组织miR-146a-5p表达;生物信息学预测TRIP6 3’-UTR区潜在结合位点,双荧光素酶报告基因实验验证;Western blot检测心肌组织TRIP6表达。建立心肌细胞缺氧复氧模型,Western blot检测给予miR-146a-5p抑制剂后沉默TRIP6对心肌细胞线粒体凋亡相关蛋白表达的影响。结果 七氟烷改善心肌缺血再灌注大鼠心肌组织病理损伤,降低大鼠心肌组织线粒体途径细胞凋亡,降低大鼠心肌组织miR-146a-5p表达水平,TRIP6 3′-UTR区存在miR-146a-5p的潜在结合位点,且七氟烷增加心肌缺血再灌注大鼠心肌组织TRIP6表达,沉默TRIP6逆转miR-146a-5p抑制剂对缺氧复氧心肌细胞线粒体凋亡相关蛋白表达的抑制作用。结论 七氟烷对心肌缺血再灌注大鼠心肌损伤具有改善作用,且抑制心肌组织线粒体凋亡,其机制可能与抑制miR-146a-5p表达,从而促进其靶基因TRIP6表达有关。Objective To explore the ameliorative effect and possible mechanism of sevoflurane on myocardial injury in myocardial ischemia-reperfusion rats. Methods SD rats were randomly divided into sham group(Sham group),myocardial ischemia reperfusion injury group(IR group) and sevoflurane group(Sev group), with 10 rats in each group. HE staining was used to detect the pathological changes of myocardial tissue. Apoptosis was detected by TUNEL assay. The expression of mitochondria apoptosis-related proteins in myocardial tissue was detected by Western blot. The expression of miR-146a-5p in myocardial tissue was detected by qRT-PCR. Potential binding sites in TRIP6 3’-UTR region were predicted by bioinformatics and verified by dual luciferase reporter gene assay. The expression of TRIP6 in myocardial tissue was detected by Western blot. A cardiomyocyte hypoxia and reoxygenation model was established, and Western blot was used to detect the effect of TRIP6 silencing after administration of Mir-146A-5p inhibitor on the expression of apoptosinrelated proteins in cardiomyocytes. Results Sevoflurane can improve the pathological injury of myocardial tissue in myocardial ischemia-reperfusion rats, reduce the apoptosis of mitochondria pathway, and reduce the level of miR-146a-5p.TRIP6 3’-UTR region has a potential binding site of miR-146a-5p. Moreover, sevoflurane increased the expression of TRIP6 in myocardial tissue of myocardial ischemia-reperfusion rats. Silencing TRIP6 reverses the inhibitory effect of miR-146A-5p inhibitor on mitochondrial apoptosin-related protein expression in hypoxic and reoxygenated cardiomyocytes.Conclusion Sevoflurane can improve myocardial injury in myocardial ischemia-reperfusion rats and inhibit mitochondrial apoptosis in myocardial tissue, the mechanism of which may be related to the inhibition of miR-146a-5p expression, thereby promoting the expression of its target gene TRIP6.

关 键 词：七氟烷 线粒体凋亡 心肌缺血再灌注损伤 miR-146a-5p TRIP6 

分 类 号：R542.2[医药卫生—心血管疾病]