Exogenous hydrogen sulfide protects fatty liver against ischemia–reperfusion injury by regulating endoplasmic reticulum stress‐induced autophagy in macrophage through mediating the class A scavenger receptor pathway in rats

Abstract

Fatty liver disease is a disease manifested with excessive alcohol intake and obese. Importantly, hydrogen sulfide (H2S) has been revealed to participate in the progression of fatty liver; however, the underlying mechanism has not been clearly elucidated yet. In this study, we aimed to investigate the effects of exogenous H2S on fatty liver ischemia–reperfusion injury (IRI) through mediating class A scavenger receptor (SRA) pathway in rats. By determining endoplasmic reticulum stress (ERS)‐related factors, autophagy markers and apoptosis‐related factors in liver tissue and liver function, levels of oxidative stress, inflammatory factors, and hepatocyte apoptosis, the effects of H2S on IRI‐induced autophagy, oxidative stress, and inflammation were all examined in rat model of fatty liver IRI. Results from obtained data showed that H2S decreased the expression of SRA, Grp78, PERK, CHOP, and Caspase‐3, and increased that of LC3‐II/LC3‐I, in addition to alleviating the pathological changes of liver and reducing the levels of ALT, AST, LDH TBARS, and MDA. Moreover, H2S decreased the levels of oxidative stress, the expression of pro‐inflammatory factors including tumor necrosis factor α, interleukin 1, and interleukin 6, and the apoptosis of hepatocytes. Our findings suggested exogenous H2S could reduce ERS by mediating the SRA pathway and protect liver function by inducing autophagy, and protect against IRI by reducing oxidative stress and inflammation.