Protective effects and mechanism of senescence marker protein 30 against diabetic cardiomyopathy
Objective To observe the protective effect of senescence marker protein 30(SMP30)against diabetic cardiomyopathy and explore its mechanism.Methods A mouse model of diabetic cardiomyopathy was established by intraperitoneal injection of strepto-zotocin(STZ)combined with high fat diet.Forty wild-type(WT)C57BL/6 mice were randomly divided into WT+Con group and WT+DCM group,with 20 mice in each group.Forty SMP30+/+mice were randomly divided into SMP30+/++Con group and SMP30+/++DCM group,with 20 mice in each group.After 12 weeks,the cardiac systolic function(LVEF,LVFS)was measured by echocardiography,serum levels of CK-MB and LDH were detected by ELISA kits,the myocardial fibrosis was observed by Masson staining,the mean cross-sectional area of cardiomyocytes was evaluated by WGA staining,ROS production was evaluated by DHE staining,the expres-sion of NF-κB p65 and the co-localization of NLRP3 and ASC were observed by immunofluorescence staining,the cardiomyocyte py-roptosis rate was detected by PI staining,the mRNA expressions of FN,CTGF,ANP,BNP,IL-1β,IL-6 and TNF-α were detected by qRT-PCR,and the protein expressions of SMP30,NLRP3,ASC,IL-1β,IL-18 and cleaved caspase-1 were detected by Western blot.Results Compared with WT+Con group,the values of LVEF and LVFS were decreased(P<0.01),serum levels of CK-MB and LDH were increased(P<0.01),the myocardial fibrosis and the myocardial hypertrophy were significantly aggravated(P<0.01),the myocardial fluorescent expression of NF-κB and ROS generation were enhanced(P<0.01),the mRNA expressions of IL-1β,IL-6,and TNF-α were increased(P<0.01),the inflammasome formation was increased(P<0.01),and the pyroptosis rate and the protein expressions of IL-1β,IL-18 and cleaved caspase-1 were upregulated in WT+DCM group(P<0.01).Compared with WT+DCM group,the values of LVEF and LVFS were increased(P<0.01),serum levels of CK-MB and LDH were decreased(P<0.01),the myocardial fibrosis and the myocardial hypertrophy were significantly relieved(P<0.01),the myocardial fluorescent expression of NF-κB and ROS generation were weakened(P<0.01),the mRNA expressions of IL-1β,IL-6,and TNF-α were decreased(P<0.01),the inflam-masome formation was decreased(P<0.01),and the pyroptosis rate and the protein expressions of IL-1β,IL-18 and cleaved caspase-1 were downregulated in SMP30+/++DCM group(P<0.01).Conclusion SMP30 can reduce the cardiomyocyte pyroptosis by inhibiting the formation of inflammasome,thereby alleviating myocardial injury in mice with diabetic cardiomyopathy.
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