山西医科大学学报2024，Vol.55Issue(9)：1144-1153,10.DOI:10.13753/j.issn.1007-6611.2024.09.007
衰老标记蛋白30对糖尿病心肌病的保护作用及其机制
Protective effects and mechanism of senescence marker protein 30 against diabetic cardiomyopathy
摘要
Abstract
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.关键词
衰老标记蛋白30/糖尿病心肌病/心肌损伤/炎症/炎症小体/细胞焦亡Key words
SMP30/diabetic cardiomyopathy/myocardial injury/inflammation/inflammasome/pyroptosis分类
医药卫生引用本文复制引用
胡培静,张学丹,杜占奎,屈欣怡,安慧仙,曹彪..衰老标记蛋白30对糖尿病心肌病的保护作用及其机制[J].山西医科大学学报,2024,55(9):1144-1153,10.基金项目
陕西省重点研发计划项目(2023-YBSF-576) （2023-YBSF-576）
