The Effect Of Caloric Restriction On Acute Rejection Of Liver Transplantation In Rats

Objectives:To explore the effect of caloric restriction on acute rejection of liver transplantation and the possible molecular mechanisms.Methods:The rat model of acute rejection after liver transplantation(SD→Wistar)was established by the classical "two-cuff" method.The receptors were divided into two groups postoperatively.ALgroup:rats were free to eat and drink after surgery without any dietary intervention.CR group:rats were given 40%calorie restriction after surgery and free to drink after surgery.Serum of each group were collected on the fifth day after surgery to detect the expression levels of IL-2,IL-4,IL-6,IL-10,IL-12,TNF-α,DBIL,IBIL,ALT and AST.Liver tissues were collected to detect the acute rejection and the expression of PPARa and TNFRSF21 in each group.Finally,bioinformatics analysis was used to explore the possible molecular mechanism of the effect of caloric restriction on acute liver transplantation rejection.Results:In the acute rejection of liver transplantation,compared with the AL group,the expressions of pro-rejection factors of IL-2,IL-6,IL-12 and TNF-α were down-regulated in the CR group,and the expressions of anti-rejection factors of IL-4 and IL-10 were also down-regulated.There was no significant difference in the expression of DBIL,IBIL,ALT and AST between the two groups.Histopathological techniques showed less inflammatory cell infiltration,less cholangitis and phlebitis,and less rejection in CR group.Compared with AL group,the expressions of PPARα and TNFRSF21 in liver in CR group were significantly up-regulated.Conclusions:Calorie restriction,to some extent,can alleviate the acute rejection after liver transplantation through the combined regulation of inflammatory response and immune tolerance,rather than a single regulation of one system.The improvement of acute liver transplantation rejection by caloric restriction may be mediated by AMPK-PPARα-TNFRSF21 pathway.