miR-30b通过抑制NLRP3炎症小体激活降低心肌缺血再灌注损伤研究

doi:10.3969/j.issn.1006-6233.2024.03.09

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Abstract Objective: To investigate the mechanism of miR-30b in alleviating myocardial injury in rats with myocardial ischemia-reperfusion (MI/R) by targeting and inhibiting the activation of NLRP3 inflammasome.Methods: Fifty SD rats were selected for inclusion in the study and randomly divided into Sham group (sham surgery group), MIRI group (model group), miR-30b mimics group (miR-30b overexpression group), CY-09 group (NLRP3 signaling pathway inhibitor group), miR-30b+CY-09 group (miR-30b overexpression+NLRP3 signaling pathway inhibitor group), with 10 rats in each group; RT-PCR was used to detect the relative expression of miR-30b in the myocardial tissue of rats in each group; Echocardiography was used to detect rat cardiac function parameters (LVEDP, LVSP,+dp/dtmax, - dp/dtmax); ELISA was used to detect the levels of myocardial tissue damage markers (CK-MB, LDH, cTnI) in rats; HE staining was used to analyze the pathological morphology of rat myocardial tissue; TUNEL method was used to detect myocardial cell apoptosis in rats; Western-blot was used to detect the expression of NLRP3 signaling pathway related proteins NLRP3, ASC, and Caspase-1 in myocardial inflammasome. Results: Compared with the Sham group, the MIRI model downregulated the mRNA expression of miR-30b in rat myocardial tissue (P<0.05). Overexpression of miR-30b upregulated the mRNA expression of miR-30b in rat myocardial tissue (P<0.05). Compared with the Sham group, the establishment of the MIRI model upregulated the levels of cardiac function parameters LVEDP, myocardial injury factors (CK-MB, LDH, cTnI), and myocardial cell apoptosis ability, and downregulated the cardiac function parameters (LVSP,+dp/dtmax,-dp/dtmax) (P<0.05). Both miR-30b overexpression plasmid transfection and NLRP3 signaling pathway blockade could downregulate the levels of cardiac function parameters LVEDP, myocardial injury factors (CK-MB, LDH, cTnI), and myocardial cell apoptosis ability, and upregulate the cardiac function parameters (LVSP,+dp/dtmax,-dp/dtmax) (P<0.05). The combination of the two could further downregulate the levels of cardiac function parameters LVEDP, myocardial injury factors (CK-MB, LDH, cTnI), and myocardial cell apoptosis ability, and upregulate cardiac function parameters (LVSP,+dp/dtmax, - dp/dtmax) (P<0.05). The myocardial morphology of Sham group rats was relatively normal. The establishment of the MIRI model could lead to disordered arrangement of myocardial tissue, resulting in myocardial fiber breakage, myocardial cell vacuolization, and inflammatory cell infiltration. Transfection of miR-30b overexpression plasmid and blockade of NLRP3 signaling pathway could improve the pathological morphology of myocardial tissue in MIRI rats, and the combination of the two groups had the greatest improvement in myocardial morphology in rats. Compared with the Sham group, the establishment of the MIRI model upregulated the expression of key proteins NLRP3, ASC, and Caspase-1 in the NLPR3 inflammasome signaling pathway in rat myocardial tissue (P<0.05). Transfection of miR-30b overexpression plasmid and blockade of NLRP3 signaling pathway downregulated the expression of NLRP3, ASC, and Caspase-1 in rat myocardial tissue (P<0.05). The combination of the two could further reduce the expression of NLRP3, ASC, and Caspase-1 in rat myocardial tissue (P<0.05). Conclusion: miR-30b improves the manifestations of cardiac dysfunction and myocardial cell damage caused by ischemia-reperfusion injury by targeting the activation of NLPR3 inflammasomes, and has a protective effect on myocardial tissue after ischemia-reperfusion injury. It is worth further clinical researching.

Key words： Myocardial ischemia-reperfusion injury miR-30b NLRP3 inflammasome signaling pathway

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http://www.hbyxzzs.cn/EN/10.3969/j.issn.1006-6233.2024.03.09 OR http://www.hbyxzzs.cn/EN/Y2024/V30/I3/398

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