机构地区:[1]河北省邯郸市第一医院心内二科,邯郸056002 [2]河北省邯郸市第一医院检验科,邯郸056002 [3]河北省邯郸市第一医院新生儿科,邯郸056002
出 处:《广西医科大学学报》2023年第7期1123-1131,共9页Journal of Guangxi Medical University
基 金:河北省卫生厅医学科学研究重点课题计划项目(No.20160335);邯郸市科学技术研究与发展计划项目(No.1623208064-5)。
摘 要:目的:探讨长链非编码RNA miR-22宿主基因(lncRNA MIR22HG)调节miR-132-3p/Toll样受体2(TLR2)轴对急性心肌梗死(AMI)小鼠心肌细胞凋亡和心室重构的影响。方法:取C57BL/6J小鼠随机分为sham组、AMI组、AMI+sh-NC组、AMI+shMIR22HG组、AMI+sh-MIR22HG+antagomir-NC组、AMI+sh-MIR22HG+antagomir-132-3p组,每组10只,除去sham组外,其它组都进行冠状动脉左前降支结扎,sham组只开胸不结扎冠状动脉,其中AMI+sh-NC组、AMI+sh-MIR22HG组、AMI+shMIR22HG+antagomir-NC组、AMI+sh-MIR22HG+antagomir-132-3p组小鼠分别相对应的对尾静脉注射sh-NC、sh-MIR22HG、sh-MIR22HG+antagomir-NC、sh-MIR22HG+antagomir-132-3p。超声心动图评估小鼠心室重构和心脏功能;HE染色和Masson染色观察心肌组织病理学变化及纤维化;RT-qPCR检测心肌组织MIR22HG、miR-132-3p表达;TUNEL法检测心肌细胞凋亡;Western blotting检测心肌组织B细胞淋巴瘤-2(Bcl-2)、激活型半胱氨酸蛋白酶-3(cleved caspase-3)/半胱氨酸蛋白酶-3(caspase-3)、Ⅰ型胶原蛋白(collagenⅠ)、collagenⅢ和α-平滑肌肌动蛋白(α-SMA)表达;双荧光素酶报告基因实验分别验证MIR22HG和miR-132-3p、miR-132-3p和TLR2的关系。结果:与sham组比较,AMI组小鼠心功能显著降低,心肌组织损伤、心肌纤维化加重,心肌细胞凋亡率、MIR22HG、TLR2、cleved caspase-3/caspase-3、collagenⅠ、collagenⅢ和α-SMA蛋白表达水平显著升高,miR-132-3p和Bcl-2蛋白表达降低(P<0.05);与AMI+sh-NC组比较,AMI+sh-MIR22HG组小鼠心功能改善,心肌组织损伤、心肌纤维化减轻,心肌细胞凋亡率、MIR22HG、TLR2、cleved caspase-3/caspase-3、collagenⅠ、collagenⅢ和α-SMA蛋白表达水平显著降低,miR-132-3p和Bcl-2蛋白表达上升(P<0.05);下调miR-132-3p减弱了敲减MIR22HG对心肌组织的保护作用;双荧光素酶报告基因实验结果显示,MIR22HG靶向调控miR-132-3p表达,miR-132-3p靶向负调控TLR2表达。结论:抑制MIR22HG表达可通过调节miR-132-3p/TLR2轴抑制AMI�Objective:To explore the influences of long non-coding RNA miR-22 host gene(lncRNA MIR-22HG)on cardiomyocyte apoptosis and ventricular remodeling in mice with acute myocardial infarction(AMI)by regulating miR-132-3p/Toll-like receptor 2(TLR2)axis.Methods:C57BL/6J mice were randomly grouped into sham group,AMI group,AMI+sh-NC group,AMI+sh-MIR22HG group,AMI+sh-MIR22HG+antagomir-NC group,and AMI+sh-MIR22HG+antagomir-132-3p group,with 10 in each group.Except that the sham group only underwent thoracotomy without coronary artery ligation,all the other groups underwent ligation of the left anterior descending coronary artery.Among them,mice in the AMI+sh-NC group,AMI+sh-MIR22HG group,AMI+sh-MIR22HG+antagomir-NC group,and AMI+sh-MIR22HG+antagomir-132-3p group were injected with sh-NC,sh-MIR22HG,sh-MIR22HG+antagomir-NC,and sh-MIR22HG+antagomir-132-3p corresponding to the tail vein,respectively.Echocardiography was used to assess ventricular remodeling and cardiac function in protease-3(cleved caspase-3)/cysteine protease-3(caspase-3),typeⅠcollagen(collagenⅠ)I,collagenⅢandα-smooth muscle actin(α-SMA);and dual-luciferase reporter assays were applied to verify the relationship between MIR22HG and miR-132-3p,miR-132-3p and TLR2,respectively.Results:Compared with the sham group,the cardiac function of the mice in the AMI group obviously decreased,and myocardial tissue damage and myocardial fibrosis were aggravated.The cardiomyocyte apoptosis rate,the expressions of MIR22HG,TLR2,cleved caspase-3/caspase-3,collagenⅠ,collagenⅢandα-SMA proteins obviously increased,while the protein expressions of miR-132-3p and Bcl-2 decreased(P<0.05).Compared with the AMI+sh-NC group,the cardiac function of the mice in the AMI+sh-MIR22HG group was obviously improved,and myocardial tissue damage and myocardial fibrosis were alleviated;the cardiomyocyte apoptosis rate,the expressions of MIR22HG,TLR2,cleved caspase-3/caspase-3,collagenⅠ,collagenⅢandα-SMA proteins obviously decreased,while the protein expressions of miR-132-3p and
关 键 词:急性心肌梗死 lncRNA MIR22HG miR-132-3p TLR2 细胞凋亡 心室重构
分 类 号:R542.2[医药卫生—心血管疾病]
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