| Acute hepatic failure is a group of severe liver damage caused by various factors,its rapid onset,rapid progression and high mortality make poor prognosis.There is currently no effective treatment except for liver transplantation.But liver transplantation is restricted seriously for a variety of reasons.With the development of stem cell technology in recent years,stem cell therapy has become a new hot spot in acute liver failure.Bone marrow mesenchymal stem cells(BMSCs)have been shown that they can differentiate into hepatocyte like cells in the corresponding microenvironment and also have a better effect on liver failure.In order to study the mechanism of BMSCs' hepatoid differentiation and the mechanism for BMSCs treating liver failure,a differential protein,galectin-3(Gal-3),was screened in the microenvironment of liver failure by our teams in the early stage.Gaectin-3 is mainly produced by macrophages and is widely found in all kinds of cells in the body.Gal-3 can affect a variety of physiological and pathological processes,including apoptosis,adhesion,migration,growth,differentiation,tumor invasion,and inflammatory response and so on.Therefore,we speculate that Gal-3 may have the ability to induce hepatocyte like cells differentiation of BMSCs.In addition,a large number of studies have shown that Gal-3 is closely related to the liver.However,the specific effects,physiological and pathological processes and effects mechanisms in vivo are not yet clear.In order to confirm our guess,and the role of gal-3 and BMSCs in vivo,we will explore both in vitro and in vivo,laying a foundation for the basic research and clinical application of hepatic failure.Objective:1.Study the effect and mechanism of galectin-3 on the induction of hepatocyte-like cells differentiation of BMSCs in rats in vitro.2.The effect and mechanism of gal-3 and BMSCs on liver failure in rats were preliminarily explored by using rat model of acute hepatic failure.Method:1.Extract and purify the femoral bone marrow stem cells of SD rats and identify them;The control group and induction group were set up,and the induction group was induced by gal-3,HGF and both of them.Cell morphology,gene expression and glycogen staining were observed at different time periods2.The model of hepatic failure was established by injecting d-galactose into the abdominal cavity of SD rats.The rats were divided into treatment groups and control group.The treatment group was divided into 6 groups by treat with gal-3,BMSCs,HGF?MCP and their combination.And then,the rats'general conditions,serum biochemical indexes and liver pathology were observed at different time points.Results:1.Compared with the control group,the cells' form of each induction group became like liver cells gradually.The induction groups'expression of ALB,CK18,AFP,M2PK,GSTP gene was positive in QPCR assay,and ALB and CK18 continued to rise,which were consistent with the results of western blot.The expression of bst-1gene gradually decreased.In each induced group,the PAS glucogen staining was positive.The combination of gal-3 and HGF was the most effective in all groups.2.The rat model of acute hepatic failure was successfully established with D-galactosamine.The mortality of rats in the control group was the highest.ALT,AST and TBIL of rats in each group gradually increased after modeling,almost all of which were highest in 2d.ALB was gradually falling,the lowest in 3d.The biochemical indexes and liver pathological conditions of each treatment group were superior to the control group.The combination of gal-3 and BMSCs was better than the treatment alone.Combined with MCP block,the effect was decreased.The effect of BMSCs+HGF+Gal-3 group rats was optimal.Conclusion:1.Gal-3 can induce BMSCs to differentiate into hepatocyte-like cells in rats,and increase the efficiency of HGF that induce BMSCs to differentiate into hepatocyte-like cells.2.Gal-3 and BMSCs can improve the liver function in acute hepatic failure rats,and the combination effect is better. |
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