Immunotherapy of tacrolimus in small volume liver transplantation of rats / 中华肝胆外科杂志

ABSTRACT

Objective To detect the plasma concentration of tacrolimus and the survival time of rats after small-volume liver transplantation,and to investigate the criteria for immunological rejection after small-volume liver transplantation.Methods Lewis rats and Brown Norway rats were used to establish a small volume and normal liver volume transplantation model,which were divided into 7 groupswhole liver transplantation group (WI),small volume allogeneic liver transplantation group (SI),and whole liver allograft group (WA),small volume allogeneic liver transplantation group (SA),whole liver allograft immunotherapy group (WAT),small volume allogeneic liver transplantation immunotherapy group (SAT),small volume allogeneic liver transplantation immunotherapy modulation group (SATa).Morphological and functional changes of liver tissue were studied postoperatively,AST and tacrolimus plasma concentrations were detected,and survival was recorded.Results Compared with the WA group,the inflammatory cells infiltrated in the portal area of the SA group,the inflammatory changes of the sinusoidal endothelial cells,and the proportion of TCRpositive lymphocytes increased.Four days after transplantation,peripheral blood tests showed that CD4+CD25+ double positive lymphocytes were significantly lower in the allograft group than in the allograft group,and the positive expression rate in the SA group (0.6％) was significantly lower than that in the WA group (1.8％).The differences were statistically significant (P＜0.05).In the SAT group,the blood concentration of tacrolimus was significantly higher than that in the WAT group at each time point (P＜0.05).The blood concentration of tacrolimus in the SATa group was relatively stable,and the plasma concentration of the SATa group was stable.And AST was significantly lower than the SAT group,the differences were statistically significant (P＜0.05).Compared with WAT group,the proliferation and apoptosis rate of hepatocytes in SAT group and SATa group were significantly increased.The proliferation of hepatocytes in SATa group was significantly higher than that in SAT group (P＜0.05).Survival analysis showed that the cumulative survival rate of the WA group was 85.7％,which was significantly higher than that of the SAT group (28.6％).The difference was statistically significant (P＜0.05).The cumulative survival rate of the SATa group was 51.7％.The survival time of WAt group was (57.4±25.0) days,SAT group was (28.0±29.10) days,SATa group was (39.7± 29.0) days,which were longer than untreated groups.The ratio of proliferation to apoptosis (PRA) increased with increasing time of tacrolimus.Regardless of blood concentration,tacrolimus plasma concentration was positively correlated with AST (R =0.758,P＜0.05),indicating RPA was inversely correlated with AST (R=-0.962,P＜0.05).Conclusion The use of tacrolimus significantly prolonged the survival time of small-volume allogeneic liver transplantation rats.Adjusting the amount of tacrolimus under the guidance of tacrolimus plasma concentration and AST serum value equation TD =-0.494TC-0.0035AST+ 260.487 to make the blood concentration relatively stable,it can further extend the allogeneic liver transplantation rat time to live.