| Purpose:To clear whether bone marrow mesenchymal stem cells (MSC) can regulate the inflammatory microenvironment in acute liver failure(ALF) by secreting cytokines, and explore the key role of Interleukin 10 (IL-10) in the process of MSC transplantation in the treatment of ALF.Methods:This experiment is divided into two parts.The first part, by studying MSC transplant and MSC conditioned medium of ALF inhibition to clear MSC regulating inflammatory microenvironment in ALF through the secretion of the inflammatory response in the cytokines. Our experiment is divided into normal group, hepatic failure group and treatment group,then observe group rats’ clinical manifestations, survival rate, liver function index, serum levels of inflammatory cytokines, liver histopathology. The experiment in the second part first detect MSC conditioned medium by protein chip to screening the effective factors, and then through the IL-10 antibodies and direct inject recombinant rat IL-10 (Recombinant Rat Interleukin-10, the rm IL-10) to clear the the key role of IL-10 in the process of MSC transplantation in the treatment of ALF, the experiment is divided into hepatic failure group, the treatment group and control group, observe each group’s clinical manifestations, survival rate, liver function index, serum levels of inflammatory cytokines, liver histopathology.Reasult:The first part of the experiment, the MSC group rats compare with liver failure group, survival rate is increased (P<0.05), serum AST, ALT, TBIL decreased significantly (P<0.05), proinflammatory factors are reduced, anti-inflammatory factors are increased (P<0.05), liver tissue damages are reliefed,cell proliferation volume increased significantly, the number of apoptosis decreased significantly (P<0.05). MSC-CM group compared with control group, survival rate is higher (P<0.05), serum AST, ALT, TBIL are decreased (P<0.05), serum proinflammatory factors are reduced,but anti-inflammatory factors increased (P<0.05), histopathological aspects,the MSC-CM group is better, cell proliferation volume increased significantly, the number of apoptosis decreased significantly (P<0.05). The second part of the experiment, protein chip testing shows the content of IL-10 is significant higher in MSC-CM (P<0.05).The MSC+anti-IL-10 group compared with MSC group, survival rate is lower (P<0.05), liver function increased significantly (P<0.05), serum proinflammatory factors are higher, anti-inflammatory factors are lower (P<0.05), the liver tissue pathology is significantly more seriously, the numbers of proliferative is obviously decreased, the number of apoptosis significantly increased (P<0.05),the rm IL-10 group compares with other two groups, survival rate increases significantly (P<0.05),serum ALT,AST,TBIL decreased obviously (P<0.05), Serum proinflammatory factors decreased significantly (P<0.05), pathologic histology is be clearly better, the number of cell proliferation, compared with the rest of the two groups increased significantly, the number of apoptosis decreases significantly (P<0.05).Conclution:MSC can effectively alleviate the rat ALF, and cytokines secreted by paracrine can regulating liver inflammatory microenvironment, among them,IL-10 secrets by MSC plays a main role, use the rmIL-10 direct injection has an obvious treatment effect, effectively reduce the liver failure rat liver function, reduce the production of proinflammatory factor, effectively relieve liver tissue pathological damage, reduce local inflammation of the liver cells, and promote the regeneration and repairment of liver injury after ALF. |
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