Resveratrol Optimizes Liver Transplantation Donor Liver Protection Plan And Mechanism

Background End-stage liver disease has become one of the most important global disease burdens,and liver transplantation is currently the most effective treatment for end-stage liver disease.However,only few patients can successfully receive liver transplantation operation due to the great shortage of liver supplement.Optimizing the strategy of liver supply protection,improving the quality of liver supply and expanding the utilization rate of marginal liver supply is the important methods to alleviate the shortage of organs at present.Hypothermic machine perfusion(HMP)is one of the hottest methods of organ preservation in recent years.Studies have shown that HMP has exerted beneficial effect on liver supply than traditional static cold storage(SCS).The optimized HMP method includes the condition optimization of the perfusion instruments,such as perfusion pressure,flow rate,and the optimization of perfusion preservation solutions.At present,the perfusion preservation solutions used in HMP research is mainly HTK solution and UW solution etc.for SCS.Previous studies have shown that resveratrol(RSV)promotes liver regeneration and protects liver function.In this study,the effects of RSV on liver supply preservation and the underlying mechanisms were investigated.Method 1)Healthy male SD mice were randomly divided into 4 groups: the SCS group(n =8):isolated liver was preserved in a histidine-tryptophan-ketoglutarate solution(HTK)solution at 0-4°c for 12 h;the HMP group(n =8): isolated liver was perfused in a HTK solution for 12 h;HTK + RSV group(n =8): isolated liver was perfused in a HTK+RSV solution for 12 h;and the HMP group: isolated liver was perfused in a HTK only solution for 12 h.(n =16):histidine-tryptophan-ketoglutarate solution(HTK)(n =8)and HTK + Resveratrol(RSV)group(n =8)for perfusion perservation for 12 h,respectively.2)Liver functions of each group were detected and the pathological changes was observed after HE staining,the malondialdehyde(MDA)and myeloperoxidase(MPO)levels in each group were evaluated.Western blot assay was used to detect the protein levels of AKT/m-TOR signaling pathway.3)At 12 hours after liver preservation,liver transplantation was performed and the changes of liver function and structure of liver tissues were detected before and after transplantation,as well as MDA and MPO.Protein levels of AKT/m TOR signaling pathway.Results 1)Compared with SCS,HMP has obvious protective effect on hepatic lobular structure and intrahepatic vascular and bile duct.2)In isolated liver preservation,HMP has better effect on protecting liver function(including ALT,AST and LDH)than SCS,mainly at 8h,10 h and 12 h time points.3)The HMP significantly reduces the levels of MDA and MPO in liver tissues;4)The HTK+RSV solution has a significant protective effect on liver function compared with the HTK solution;5)The activation of AKT/m TOR signaling pathway related proteins in the liver tissues of the HTK+RSV group is increased compared with the HTK group.6)The protective effect of HTK+RSV on liver after transplantation is superior to the HTK group.Conclusions 1)HMP is obviously superior to SCS preservation in liver transplantation organ preservation.2)The protective effect of HTK+RSV modified solution on transplanted liver is better than HTK solution.3)The protective effect of HTK+RSV modified solution on transplanted liver may be associated with activation of AKT/m-TOR signal pathway.