HIF-2α调控心肌细胞中IL-6表达对心肌缺血再灌注损伤的作用  

Effect of HIF-2α on myocardial ischemia-reperfusion injury by regulating IL-6 expression in myocardial cells

作　　者：樊蓉[1] 石永朋 李邢婷 刘世宏 FAN Rong;SHI Yong-peng;LI Xing-ting;LIU Shi-hong(Department of Cardiovascular Medicine,East Hospital,the First Affiliated Hospital of Xi'an Jiaotong University,Xi'an,Shanxi Province710089,China)

机构地区：[1]西安交通大学第一附属医院东院心血管内科,陕西西安710089

出　　处：《解剖学研究》2021年第3期226-229,235,共5页Anatomy Research

摘　　要：目的探讨缺氧诱导因子-2α(HIF-2α)调控心肌细胞中IL-6表达对心肌缺血再灌注损伤(MIRI)的作用。方法8周龄SPF级雄性C57BL/6小鼠构建MIRI模型,一部分小鼠分为对照组(注射生理盐水)和HIF-2αshRNA组(注射含HIF-2αshRNA3的生理盐水),获取小鼠心肌细胞探讨HIF-2α对IL-6的调控和对MIRI的作用;一部分小鼠分为对照组(注射生理盐水)和IL-6 shRNA组(注射含IL-6 shRNA的生理盐水),获取小鼠心肌细胞探讨IL-6对MIRI的作用。结果HIF-2αshRNA组缺氧/复氧后的心肌细胞凋亡率、心肌梗塞面积高于对照组(P<0.05);缺氧/复氧处理后的心肌细胞HIF-2α及IL-6的蛋白表达量高于常氧环境下,HIF-2αshRNA组HIF-2α、IL-6的蛋白表达量低于对照组,差异均有统计学意义(P<0.05);ChIP实验结果显示低氧状态下HIF-2α抗体募集的IL-6基因的启动区域的DNA丰富度高于常氧组(P<0.05);IL-6 shRNA组缺氧/复氧后的心肌梗塞面积大于对照组(P<0.05)。结论HIF-2α可保护心肌抗MIRI,同时参与转录调控IL-6的表达。Objective To investigate the effect of hypoxia inducible factor-2α(HIF-2α)on myocardial ischemia-reperfusion injury(MIRI)by regulating IL-6 expression in myocardial cells.Methods 8-week-old SPF male C57BL/6 mice were used to construct the MIRI model,and some mice were divided into control group(normal saline)and HIF-2αshRNA group(normal saline containing HIF-2αshRNA3).The myocardial cells were collected to analyze the effect HIF-2αon IL-6 expression and MIRI.The rest mice were divided into control group(normal saline)and IL-6 shRNA group(normal saline containing IL-6 shRNA).The myocardial cells were collected to analyze the effect IL-6 on MIRI.Results The myocardial cell apoptosis rate and myocardial infarction area after hypoxia/reoxygenation in HIF-2αshRNA group were higher than those in control group(P<0.05).The expression levels of HIF-2αand IL-6 in myocardial cells treated with hypoxia/reoxygenation were higher than those treated with normal oxygen.The protein expression of HIF-2αand IL-6 in HIF-2αshRNA group was lower than that of control group,with significant difference(P<0.05).ChIP assay showed that the DNA richness of the IL-6 promoter region recruited by HIF-2 antibody under hypoxia was higher than that in normal oxygen group(P<0.05).The area of myocardial infarction after hypoxia/reoxygenation in IL-6 shRNA group was larger than that in control group(P<0.05).Conclusion HIF-2αcan protect myocardium against MIRI and participate in transcriptional regulation of IL-6 expression.

关 键 词：缺氧诱导因子-2Α 白细胞介素-6 心肌缺血再灌注损伤 心肌细胞 

分 类 号：R542.2[医药卫生—心血管疾病]