Experimental Study On The Intervention Effect Of Adipose Mesenchymal Stem Cells On Liver Fibrosis In Rats

Liver fibrosis is a damage healing response that exists in any liver injury during liver repair and healing.If the damaging factors cannot be removed for a long time,the fibrosis process will develop into cirrhosis with high mortality if it continues for a long time.Therefore,effective treatment of liver fibrosis is to prevent the occurrence of advanced liver disease.Studies have shown that hepatic stellate cells（HSC）proliferate and differentiate into extracellular matrix after stimulated and activated by pathogenic factors,resulting in large amounts of extracellular matrix deposition in liver over time and leading to liver fibrosis.Therefore,inhibiting the activation of HSC is the key to the treatment of hepatic fibrosis.Hippo signaling pathway plays a role in regulating organ size,cell proliferation and apoptosis,and is the main regulatory pathway in the proliferation and differentiation of activated HSC.Our previous studies have found that mesenchymal stem cells derived from adipose tissue（ADMSCs）can effectively alleviate tissue damage,but the role and specific mechanism of ADMSCs in liver fibrosis remain unclear.In addition,studies have shown that ADMscs have a mutual regulatory effect on Hippo signaling pathway.This study focused on the therapeutic effect of ADMSCs on hepatic fibrosis and the ability to inhibit the activation of HSC,and detected the participation of Hippo signaling pathway in the intervention process,so as to explore the specific mechanism of ADMSCs in the treatment of liver fibrosis.In this study,ADMSCs were first isolated and identified.Then,ADMSCs were injected into CCl₄ to induce liver fibrosis model rats.The ability of ADMSCs to relieve hepatic fibrosis injury and its specific mechanism were evaluated by serum biochemical detection,pathological histology,the changes in the expression levels of fibrosis factors and key factors in Hippo signaling pathway.In vitro,activated HSC were co-cultured with ADMSCs to detect the expression levels of fibrosis factors and key factors of Hippo signaling pathway in HSC,and to verify the ability of ADMSCs to inhibit HSC activation.Hippo signaling pathway inhibitors were used to treat HSC,and the changes in the expression level of fibrosis factors in the co-culture system were detected,so as to explore the role of Hippo signaling pathway in the process of ADMSCs inhibiting HSC activation.The specific results are as follows:1.The intervention effect of ADMSCs on hepatic fibrosisAfter cell transplantation,the biochemical indexes and liver fibrosis factors of the treatment group were significantly decreased compared with the model control group.The proliferation ability of HSC cells decreased significantly after cell coculture in vitro.The expression of fibrosis factor decreased obviously.2.Hippo signaling pathway is involved in the intervention of ADMSCs in hepatic fibrosisThe injection of ADMSCs showed that the YAP protein expression in the treatment group was significantly decreased compared with the model control group.The expression levels of YAP and TAZ protein in HSC co-cultured with ADMSCs decreased significantly.After Hippo signaling pathway inhibition,the decreasing trend of fibrosis factor and YAP gene expression in HSC co-cultured with ADMSCs was weaker than that in the co-culture group.These results indicated that the ability of ADMSCs to interfere with HSC activation was weakened after Hippo signaling pathway was inhibited,which proved that Hippo signaling pathway was indeed involved in the intervention of ADMSCs in HSC activation.Comprehensive analysis of the experimental results showed that ADMSCs could inhibit HSC activation by regulating Hippo signaling pathway in the treatment of liver fibrosis.This study provides a theoretical basis for studying the specific mechanism of ADMSCs in liver fibrosis.