Bone Marrow Mesenchymal Stem Cells Ameliorate GalN-induced Liver Failure In Rat Via P38/MAPK And STAT3 Signaling Pathway

Objective:l.Vertify that BMSCs ameliorate inflammatory response in ALF through secretion of cytokines.The key role is IL-10.2.Vertify that IL-10 inhibite the inflammatory response in ALF through P38/MAPK and STAT3 signaling pathway.Methods:The experiment is divided into two parts. The first part is divided into six groups.A control group, ALF group, BMSCs treatment group, MSC-CM treatment group, rmIL-10 treatment groups, anti-IL-10 antibody group. We compare the rats’ general clinical manifestations, survival rate, liver function, serum levels of inflammatory cytokines, liver pathology in rats to assess the situation of ALF. Protein microarray analysis the secretion of cytokines in MSC-CM. Through the above method,we can research the therapeutic effects of paracrine of BMSCs, and the key role ---IL-10 for ALF.The second part uses the western blot to test the P38/MAPK, STAT3 and change their phosphorylation levels in the control group, ALF Group, rm IL-10 treatment group.After the suppression of two pathways and explore each rat general clinical manifestations, survival, liver function, levels of inflammatory cytokines and liver histopathology situation. By the above method we can study P38/MAPK and STAT3 signaling pathway in the inhibit inflammation’s role in IL-10.Results:The first partial results showed BMSCs treatment group, MSC-CM treatment group, rm IL-10 treatment groups with respect to the ALF Group relieving liver failure inflammation, significantly reducing pro-inflammatory cytokines, increased IL-10 levels inhibiting inflammatory cytokines and thus facilitate hepatocyte proliferation, reduce liver cell apoptosis and promote functional recovery of liver cells, significantly reduce the role of transaminase and total bilirubin levels, lower mortality (p<0.05). Anti-IL-10ab significantly reversed the therapeutic effect of rm IL-10. Protein microarray BMSCs conditioned medium suppressing inflammatory cytokine IL-10 was the highest. The second part of the Western blot showed that ALF group, P38/MAPK abnormally high levels, reduce STAT3 levels; il-10 group P38/MAPK phosphorylation level was significantly inhibited, increased levels of STAT3 phosphorylation. Inhibition of P38/MAPK can significantly reverse the manifestations of acute liver failure, inhibits inflammation, suggesting that IL-10 by inhibiting the p38/MAPK pathway for therapeutic purposes. After STAT3 and inhibits the activity of the therapeutic effect of IL-10 are reversed, to identify IL-10 by activation of STAT3 pathway to achieve therapeutic effect. :1, Regulating inflammatory microenvironment is the treatment of BMSCs transplantation in acute liver failure.The IL-10 is their critical factor.2, IL-10 inhibites the inflammatory response in acute liver failure through inhibiting P38/MAPK pathway and activatingt the STAT3 pathway...