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

作者：Qianzhen Zhang, Chenxi Piao, Jiayuan Xu, Yue Wang, Tao Liu, Haiyang Ma, Hongbin Wang · 发表于：Journal of Cellular Physiology · 年份：2023 · DOI：10.1002/jcp.30968 · 被引用次数：20 · 研究领域：Extracellular vesicles in disease、Endoplasmic Reticulum Stress and Disease、Liver Disease and Transplantation

Hepatic 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 G...