HSP70 alleviates sepsis-induced cardiomyopathy by attenuating mitochondrial dysfunction-initiated NLRP3 inflammasome-mediated pyroptosis in cardiomyocytes

作者：Chenlu Song, Yiqiu Zhang, Qing Pei, Li Zheng, Meiyu Wang, You-zhen Shi, Shan Wu, Wei Ni, Xiujun Fu, Yinbo Peng, Wen Zhang, Min Yao · 发表于：Burns & Trauma · 年份：2022 · DOI：10.1093/burnst/tkac043 · 被引用次数：37 · 研究领域：Inflammasome and immune disorders、Heat shock proteins research、Streptococcal Infections and Treatments

Abstract Background Sepsis-induced cardiomyopathy (SIC) is an identified serious complication of sepsis that is associated with adverse outcomes and high mortality. Heat shock proteins (HSPs) have been implicated in suppressing septic inflammation. The aim of this study was to investigate whether HSP70 can attenuate cellular mitochondrial dysfunction, exuberated inflammation and inflammasome-mediated pyroptosis for SIC intervention. Methods Mice with cecal ligation plus perforation (CLP) and lipopolysaccharide (LPS)-treated H9C2 cardiomyocytes were used as models of SIC. The mouse survival rate, gross profile, cardiac function, pathological changes and mitochondrial function were observed by photography, echocardiography, hematoxylin–eosin staining and transmission electron microscopy. In addition, cell proliferation and the levels of cardiac troponin I (cTnI), interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) were determined by Cell Counting Kit-8, crystal violet staining and enzyme-linked immunosorbent assay. Moreover, mitochondrial membrane potential was assessed by immunofluorescence staining, and dynamin-related protein 1 and pyroptosis-related molecules [nucleotide-binding domain, leucine-rich-repeat containing family pyrin domain-containing 3 (NLRP3), caspase-1, gasdermin-D (GSDMD), gasdermin-D N-terminal (GSDMD-N)] were measured by western blotting, immunoprecipitation and immunoblotting. Finally, hsp70.1 knockout mice with CLP were used to verify the effects...