山西医科大学学报2023，Vol.54Issue(12)：1562-1571,10.DOI:10.13753/j.issn.1007-6611.2023.12.003
miR-145-5p对脓毒症小鼠心肌损伤的保护作用及其机制
Protective effect and mechanism of miR-145-5p against sepsis-induced myocardial injury
摘要
Abstract
Objective To investigate the protective effects and mechanism of miR-145-5p against the sepsis-induced myocardial injury.Methods Eighty male C57BL/6 mice were randomly divided into sham+ago-NC group,sham+ago-miR group,CLP+ago-NC group and CLP+ago-miR group,with 20 mice in each group.A mouse sepsis model was established by cecal ligation and puncture(CLP).The survival rate was calculated.The serum CK-MB and cTnI levels and the expressions of IL-1β,IL-6,and TNF-α were detected by ELISA kits.The microscopic structure of myocardial tissue was observed by HE staining.The cardiac systolic function(LVEF and LVFS)was measured by echocardiography.The expressions of CD68,Ly6G,NLRP3,and ASC were detected by immuno-fluorescence staining.The cardiomyocyte pyroptosis was observed by PI staining.The mRNA expression of miR-145-5p was detected by qRT-PCR.The protein expressions of NLRP3,ASC,cleaved Caspase-1,IL-18,and N-GSDMD were detected by Western blot.Results Compared with sham+ago-NC group,the survival rate was significantly decreased in CLP+ago-NC group(P＜0.001),the levels of CK-MB and cTnI were significantly increased(P＜0.01),the myocardial fibers were disordered and obviously broken,and LVEF and LVFS were significantly reduced(P＜0.01).Compared with sham+ago-NC group,myocardial CD68-positive macrophages and Ly6G-positive neutrophils were significantly increased(P＜0.01),the expressions of IL-1 β,IL-6 and TNF-α were significantly up-regulated(P＜0.01),and the myocardial inflammasome and the cardiomyocyte pyroptosis were significantly increased in CLP+ago-NC group(P＜0.01).Compared with CLP+ago-NC group,the survival rate was significantly increased in CLP+ago-miR group(P＜0.05),the levels of CK-MB and cTnI were significantly decreased(P＜0.01),the myocardial fiber disturbance and rupture was significantly reduced,and LVEF and LVFS values were significantly increased(P＜0.01).Additionally,compared with CLP+ago-NC group,myocardial macrophages and neutrophils were significantly reduced(P＜0.01),the expressions of IL-1β,IL-6 and TNF-α were signifi-cantly downregulated(P＜0.01),and the myocardial inflammasome and the cardiomyocyte pyroptosis were significantly decreased in CLP+ago-miR group(P＜0.01).Conclusion Overexpression of miR-145-5p can improve the cardiac function by inhibiting myocar-dial inflammation and cardiomyocyte pyroptosis,thus playing a protective role against sepsis-induced myocardial injury.关键词
miR-145-5p/脓毒症/心肌损伤/炎症/焦亡Key words
miR-145-5p/sepsis/myocardial injury/inflammation/pyroptosis分类
医药卫生引用本文复制引用
胡培静,张学丹,屈欣怡,李炜,曹彪..miR-145-5p对脓毒症小鼠心肌损伤的保护作用及其机制[J].山西医科大学学报,2023,54(12):1562-1571,10.基金项目
陕西省重点研发计划项目(S2022-YF-YBSF-0781) （S2022-YF-YBSF-0781）
