Optimized postconditioning algorithm protects liver graft after liver transplantation in rats  

作　　者：Jian-Hui Li Jun-Jun Jia Wen Shen Sha-Sha Chen Li Jiang Hai-Yang Xie Lin Zhou Shu-Sen Zheng 

机构地区：[1]Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery First Affiliated Hospital, Zhejiang Univeristy School of Medicine, Hangzhou 310003, China [2]NHFPC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou 310003, China [3]Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, China [4]Zhejiang Chinese Medical University, Hangzhou 310053, China [5]Department of Anesthesia, First Affiliated Hospital, Zhejiang Univeristy School of Medicine, Hangzhou 310003, China

出　　处：《Hepatobiliary & Pancreatic Diseases International》2018年第1期32-38,共7页国际肝胆胰疾病杂志（英文版）

基　　金：supported by grants from Foundation for Innovative Research Groups of the National Natural Science Foundation of China(81421062);National Natural Science Foundation of China(81470891);863 National High Technology Research and Development Program of China for Young Scientist(2015AA020923);Public Technology Research and Social Development Projects(2016C33145);China Postdoctoral Science Foundation(2017M610374)

摘　　要：Background: Ischemia reperfusion injury(IRI) causes postoperative complications and influences the outcome of the patients undergoing liver surgery and transplantation. Postconditioning(Post C) is a known manual conditioning to decrease the hepatic IRI. Here we aimed to optimize the applicable Post C protocols and investigate the potential protective mechanism.Methods: Thirty Sprague–Dawley rats were randomly divided into 3 groups: the sham group(n = 5),standard orthotopic liver transplantation group(OLT, n = 5), Post C group(OLT followed by clamping and re-opening the portal vein for different time intervals, n = 20). Post C group was then subdivided into 4 groups according to the different time intervals:(10 s × 3, 10 s × 6, 30 s × 3, 60 s × 3, n = 5 in each subgroup). Liver function, histopathology, malondialdehyde(MDA), myeloperoxidase(MPO), expressions of p-Akt and endoplasmic reticulum stress(ERS) related genes were evaluated.Results: Compared to the OLT group, the grafts subjected to Post C algorithm(without significant prolonging the total ischemic time) especially with short stimulus and more cycles(10 s × 6) showed significant alleviation of morphological damage and graft function. Besides, the production of reactive oxidative agents(MDA) and neutrophil infiltration(MPO) were significantly depressed by Post C algorithm. Most of ERS related genes were down-regulated by Post C(10 s × 6), especially ATF4, Casp12, hspa4, ATF6 and ELF2, while p-Akt was up-regulated.Conclusions: Post C algorithm, especially 10 s × 6 algorithm, showed to be effective against rat liver graft IRI. These protective effects may be associated with its antioxidant, inhibition of ERS and activation of p-Akt expression of reperfusion injury salvage kinase pathway.Background: Ischemia reperfusion injury(IRI) causes postoperative complications and influences the outcome of the patients undergoing liver surgery and transplantation. Postconditioning(Post C) is a known manual conditioning to decrease the hepatic IRI. Here we aimed to optimize the applicable Post C protocols and investigate the potential protective mechanism.Methods: Thirty Sprague–Dawley rats were randomly divided into 3 groups: the sham group(n = 5),standard orthotopic liver transplantation group(OLT, n = 5), Post C group(OLT followed by clamping and re-opening the portal vein for different time intervals, n = 20). Post C group was then subdivided into 4 groups according to the different time intervals:(10 s × 3, 10 s × 6, 30 s × 3, 60 s × 3, n = 5 in each subgroup). Liver function, histopathology, malondialdehyde(MDA), myeloperoxidase(MPO), expressions of p-Akt and endoplasmic reticulum stress(ERS) related genes were evaluated.Results: Compared to the OLT group, the grafts subjected to Post C algorithm(without significant prolonging the total ischemic time) especially with short stimulus and more cycles(10 s × 6) showed significant alleviation of morphological damage and graft function. Besides, the production of reactive oxidative agents(MDA) and neutrophil infiltration(MPO) were significantly depressed by Post C algorithm. Most of ERS related genes were down-regulated by Post C(10 s × 6), especially ATF4, Casp12, hspa4, ATF6 and ELF2, while p-Akt was up-regulated.Conclusions: Post C algorithm, especially 10 s × 6 algorithm, showed to be effective against rat liver graft IRI. These protective effects may be associated with its antioxidant, inhibition of ERS and activation of p-Akt expression of reperfusion injury salvage kinase pathway.

关 键 词：Liver transplantation Ischemia reperfusion injury POSTCONDITIONING 

分 类 号：R[医药卫生]