Immunosuppressive Regimens On Renal Function And Metabolic Mechanism Of The Population With Different Glucose Metabolism Before And After Renal Transplantation

Objective: The aim of this study is to investigate the effect on renal function and metabolic indexes with different immunosuppressive regimens of Cs A and FK506 before and after renal transplantation in normal glucose tolerance patients, impaired glucose tolerance patients and diabetes mellitus patients.And analyse the pathological changes and physical and chemical effection on kidney in diabetic rats caused by Cs A and FK506.Methods: Clinical trials:a clinical trial in 312 patients with renal transplantation from February 2009 to February 2014 in Tianjin First Central Hospital were retrospectively analyzed. According to the different immunosuppression of the selected cases were divided into Cs A group and FK506 group, wherein each group according to the preoperative OGTT diagnosis standard is divided into: NGT group, IGT group and DM group. Collect and analysis before and after the operation, after 6 months and 1 years of the Cs A concentration, FK506 concentration,BMI, glucose tolerance and insulin function, HOMA-IR, liver function, renal function, blood lipid, IL-6 and other metabolic indexes. And analyse the incidence of PTDM in NGT and IGT group, the incidence of acute rejection and other adverse reaction rate. Basic experiment: the rats were randomly divided into 5 groups: control group, DM group, DM+FK506 0.5 mg / kg group, DM+FK506 1 mg / kg group and cyclosporin A group, l0 in each group, a total of observation of 4 weeks. Detect the levels of blood glucose, AER, Ccr, IL-6 and pathological changes of renal tissue.Detect the expression of Ca N in kidney tissue, TGF-β1and NF-κB.Results: Clinical trials:The incidence of acute rejection is 9.09% in Cs A group and is 4.76% in FK506 group, there is significant difference(P <0.05). The incidence of PTDM in NGT and IGT group 1 year after transplantation in FK506 group and Cs A group are 11.8% and 3.2%, there is significant difference(P <0.05).The level of IL-6 in DM group is significantly higher than the control group, the group in high incidence in PTDM has the high level of IL-6,and is positively correlated with HOMA-IR. The recovery of renal function is better in FK506 group than in Cs A group, there is significant difference(P <0.05).The incidence of liver damage, hypertension and hyperlipidemia is lower in FK506 group than in Cs A group, there is significant difference(P <0.05).Basic experiment: FK506 than Cs A is more likely to increase blood glucose level and decrease glucose tolerance. The decrease of AER and Ccr is more obvious in DM+FK506 1.0 group than in DM+FK506 0.5 groups, there is significant difference(P <0.05),but between DM+FK506 1.0 group and DM+Cs A group in AER and Ccr, the difference was not statistically significant(P >0.05). Both Cs A and FK506 can significantly inhibit the expression of renal tissue of diabetic model of elevated Ca N protein, especially in DM+FK506 1.0 group and DM+Cs A group than in DM+FK506 0.5 group(P <0.05).The control group rats glomerular and renal tubulointerstitial has a small amount of TGF-β1 expression. The expression of TGF- β 1 protein expression in glomerular and tubulointerstitial is significantly higher in DM group than in control group(P <0.01). The expression of TGF-β1 protein expression in glomerular and tubulointerstitial is lower in DM+FK506 0.5group, DM+FK506 1.0 group and DM+Cs A group than in DM group(P <0.05,0.01,0.01),but the expression of TGF-β1 protein in glomerular and tubulointerstitial is higher in DM+FK506 0.5 group than in control group(P <0.05).The expression of NF-κB and IL-6 protein is higher in DM group than other 4 groups(P <0.05),but there is no difference in DM+FK506 0.5 group, DM+FK506 1.0 group and DM+Cs A group(P >0.05).Conclusion: Clinical trials: FK506 group compared with Cs A group is more likely to increase Hb A1 c, HOMA-IR, triglyceride and total cholesterol.The incidence of PTDM is higher in FK506 group than in Cs A group.Because of low immunity, PTDM can lead to an increased risk of infection. The recovery of renal function is better in FK506 group than in Cs A group.The incidence of liver damage, hypertension and hyperlipidemia is lower in FK506 group than in Cs A group.Basic experiment: FK506 than Cs A is more likely to increase blood glucose level and decrease glucose tolerance. The decrease of AER and Ccr is more obvious in DM+FK506 1.0 group than in DM+FK506 0.5 groups. Both Cs A and FK506 can significantly inhibit the expression of renal tissue of diabetic model of elevated Ca N protein, especially in DM+FK506 1.0 group and DM+Cs A group. The expression of TGF-β1 protein expression in glomerular and tubulointerstitial is higher in DM group than in control group The expression of TGF-β1 protein expression in glomerular and tubulointerstitial is lower in DM+FK506 0.5 group, DM+FK506 1.0 group and DM+Cs A group than in DM group,but the expression of TGF-β1 protein in glomerular and tubulointerstitial is higher in DM+FK506 0.5 group than in control group.The expression of NF-κB and IL-6 protein is higher in DM group than other 4 groups,but there is no difference in DM+FK506 0.5 group, DM+FK506 1.0 group and DM+Cs A group.