Hydrogen Sulfide Attenuates Sepsis-Induced Cardiomyopathy by Inhibiting Endoplasmic Reticulum Stress in Rats

Lei Li, Lichun Guo, Guodong Cao, Xin Peng, Qinghong Cheng

Article ID: 7067
Vol 37, Issue 1, 2023
DOI: https://doi.org/10.23812/j.biol.regul.homeost.agents.20233701.18
Received: 8 February 2023; Accepted: 8 February 2023; Available online: 8 February 2023; Issue release: 8 February 2023

Abstract

Background: Existing studies have found that hydrogen sulfide (H2S) can alleviate heart damage caused by sepsis. The dynamic unbalance due to stress and inflammation in endoplasmic reticulum function will cause endoplasmic reticulum stress (ERS), which is related to sepsis. However, it remains unclear whether H2S reduces sepsis-induced heart damage by down-regulating cardiac ERS. Metheods: In this study, sepsis was induced in rats by cecal ligation and puncture (CLP). Cardiac enzymes were determined by biochemical analyzers. ELISA kits were used to detect inflammatory cytokine and histopathology and assess the histological characteristics of myocardial tissue. In addition, the myocardial injury was assessed by the TUNEL (TdT-mediated dUTP nick-end labeling) technique. The expression of the relative protein was tested by western blot. Results: Our study demonstrated attenuation of myocardial enzyme levels and inflammatory factors tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) levels by H2S in rats with sepsis while that of interleukin-10 (IL-10) was increased. Histopathological examinations indicated that the use of H2S reduced myocardial tissue damage and myocardial apoptosis rate. Western blot analysis suggested significantly reduced expression of 78 kDa glucose-regulated protein (GRP78), C/EBP-homologous protein (CHOP), and cleaved caspase-12 by H2S, indicating inhibition of ERS. The expressions of proapoptotic factors Bax, cleaved caspase-3, the inflammatory factor, and nuclear factor kappa-B (NF-κB) were decreased by H2S. The expression of B-cell lymphoma-2 (Bcl-2) was increased by H2S, indicating alleviation of cardiomyocyte apoptosis and inflammation. Conclusions: Overall, our results suggest that alleviating sepsis-induced myocardial damage could be achieved by H2S via restraining ERS in rats.


Keywords

hydrogen sulfide;endoplasmic reticulum stress;heart dysfunction;sepsis


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