| This study was to establish a rat model of diabetic sepsis,by observing the histological changes of the ileum,the peripheral endotoxin translocation,the apoptosis of mesenteric lymphocytes and the expression of PD-1/PD-L1 protein in the lyphocytes of rats in different group.To investigate the effect of BMSCs on intestinal mucosal barrier in rats,in order to further explore its potential application,and to provide a new theoretical basis for the treatment of sepsis.Chapter one:Establish model and analysis survival of diabetic sepsis ratObjective and method:To establish a rat model of diabetic sepsis and study the effect of bone marrow mesenchymal stem cells on the diabetic sepsis rats by the survival curve.The main results:1.Compared with normal rats,T2DM rats injected STZ 3D,7d,14d and 2d blood glucose level was significantly higher than that of normal rats(P<0.01).2.The plasma level of TNF-α in BMSCs group was significantly higher than that of Control group and Sham group,but lower than CLP+Saline group(P<0.05);while the plasma level of IL-10 in BMSCs group was higher than that of CLP+Saline group(P<0.05);3.The median survival time of BMSCs group 44h was higher than that of CLP+Saline group 58h.Conclusion:The results showed that BMSCs could decrease the level of inflammatory cytokines in rats with sepsis and improve rat survival.Chapter two:The effects of BMSCs on intestinal mucosal barrier in diabetic rats with sepsis.Objective and method:The effect of BMSCs on intestinal mucosal barrier function in diabetic rats with sepsis was determined by detecting the histopathological changes in intestines and measuring the level of plasma endotoxin(LPS)and diamine oxidas(DAO).The main results:1.The intestinal pathologic injury in group BMSCs+CLP was light than CLP+Saline group.2.The levels of plasma DAO and LPS were reduce in group BMSCs+CLP.And compare with CLP+Saline group,the levels of plasma DAO and LPS in the 12h time points were significantly reduce(P<0.05).3.The correlation analysis showed that the height and area of small intestinal villi was negatively correlated with plasma DAO and LPS(P<0.05).Conclusion:BMSCs has a protective effect on intestinal mucosal barrier in rats with diabetic sepsis,which can reduce the intestinal mucosal barrier injury.Chapter three:Protective effects of BMSCs on intestinal mucosa in rats with diabetic sepsis and its possible mechanism.Objective and method:To explore the possible mechanism of the protective effect of BMSCs on intestinal immune barrier,we detecting the inflammatory cytokines in intestinal,the level of slgA in jejunal and the function of mesenteric lymph nodes changes.The main results:1.The levels of inflammatory cytokines(IFN-γ、TNF-α and LPS)in intestinal was decreased in BMSCs+CLP group;while the level of IL-10 has increased(P<0.05).2.The level of total slgA has increased in BMSCs+CLP group;while the level of free slgA was decreased compared with CLP+Saline(P<0.05).3.Compared with CLP+Saline group,the apoptosis rate of intestinal lymphocytes was significantly decreased in BMSCs+CLP group(P<0.05);and the expression intensity of PD-1 on the surface of lymphocyte membrane was obviously increased.Conclusion:BMSCs can inhibit the apoptosis of lymphocytes and maintain the expression of PD-1 on lymphocytes membrane,which plays a key role in recovery of intestinal immunity. |
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