Exploring The Changes Of PTEN And Smad7 Methylation In The Treatment Of Liver Fibrosis With BMSCs

Obejective:The aim of this study was to investigate the changes of PTEN and Smad7methylation and their mechanisms in the treatment of liver fibrosis with bone marrow mesenchymal stem cells（BMSCs）.Methods:Rats were intraperitoneally injected with normal saline for 6 weeks as a control group（6 rats）,we used a pathological rat model of liver fibrosis that was induced by treatment with carbon tetrachloride（CCl₄）and vegetable oil.for 6 weeks.The pathological rats were divided into model group（6 rats）,BMSCs group（6 rats）,DNMTs inhibitor group（18 rats）,and combined group（6 rats）.The control group and model group were injected intravenously in the portal vein with 0.5 ml PBS,The BMSCs group and the combined group were injected intravenously in the portal vein with 0.5 ml cultured mesenchymal stem cells isolated from male rats at a dose of 3×106 MSCs per rat suspended in PBS,The DNMTs inhibitor group were intraperitoneally injected with of 1,3and 5 mg·kg–1 of 5-aza-2’-deoxycytidine（5-azadC）.The combined treatment group were injected the optimal therapeutic concentration.After three weeks of treatment,the rats were sacrificed and liver tissue and blood samples were harvested for further analysis.Results:The analysis revealed that PTEN and Smad7 methylation was hypermethylated and its expression was down-regulated in model group,The PTEN and Smad7 methylation was demethylated and its expression was up-regulated in BMSCs group,DNMTs inhibitor group and combined group.Compared with the model group.The rats showed a significan reduction in the plasma aspartate aminotransferase（AST）alanine aminotransferase（ALT）and total bilirubin（T-Bil）.Conclusion:The repair ability of BMSCs on liver fibrosis can through the P13K/AKT pathways by PTEN and through the TGF-β/Smad pathway by Smad7.