ADSCs‐exo attenuates hepatic ischemia–reperfusion injury after hepatectomy by inhibiting endoplasmic reticulum stress and inflammation

Abstract

AbstractHepatic ischemia–reperfusion (I/R) injury commonly occurs during liver surgery. Exosomes from adipose‐derived stem cells (ADSCs‐exo) induce a hepatoprotective effect during hepatic I/R injury. This study aimed to investigate the possible mechanism by which ADSCs‐exo attenuates hepatic I/R injury in rats. Rats were randomly divided into four groups: Sham, I30R + PH, ADSCs, and ADSCs‐exo groups. Liver tissues were collected immediately after 24 h of reperfusion for further analyses. The content of inflammatory factors in liver tissue was detected using enzyme‐linked immunosorbent assay. The pathological changes in liver tissue were analyzed using HE staining. Transmission electron microscopy was used to visualize the ultrastructural changes of hepatocytes. Real‐time quantitative polymerase chain reaction (RT‐qPCR) and western blot analysis were used to detect the expression of endoplasmic reticulum stress (ERS)‐related genes and proteins. Liver histomorphology and hepatocyte ultrastructure changes improved after ADSCs‐exo treatment. Moreover, ADSCs‐exo treatment significantly downregulated tumor necrosis factor‐α, interleukin‐1β (IL‐1β), and IL‐6 levels while upregulating IL‐10 levels. Western blot analysis suggested that the protein expressions of GRP78, p‐PERK, p‐eIF2α, p‐IRE1α, XBP1s, ATF‐6, ATF‐4, CHOP, p‐JNK, cleaved‐Caspase‐3, cleaved Caspase‐9, and cleaved Caspase‐12 significantly decreased after ADSCs‐exo treatment. RT‐qPCR results demonstrated that mRNA expression of GRP78, IRE1α, XBP1, ATF‐6, ATF‐4, CHOP, JNK, Caspase‐3, Caspase‐9, and Caspase‐12 markedly reduced after ADSCs‐exo treatment. In conclusion, ADSCs‐exo protects against hepatic I/R injury after hepatectomy by inhibiting ERS and inflammation. Therefore, ADSCs‐exo can be considered as a viable option for the treatment of hepatic I/R injury.