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| Optimized postconditioning algorithm protects liver graft after liver transplantation in rats |
| Jian-Hui Li a,b, Jun-Jun Jia a,b,c, Wen Shen d, Sha-Sha Chen e, Li Jiang b, Hai-Yang Xie a,b,c, Lin Zhou a,b,c, Shu-Sen Zheng a,b,c,∗ |
a Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery First Affiliated Hospital, Zhejiang Univeristy School of Medicine, Hangzhou 310003, China
b NHFPC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou 310003, China
c Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, China
d Zhejiang Chinese Medical University, Hangzhou 310053, China
e Department of Anesthesia, First Affiliated Hospital, Zhejiang Univeristy School of Medicine, Hangzhou 310003, China
∗ Corresponding author at: Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, Zhejiang Univeristy School of Medicine, Hangzhou 310003, China.
E-mail address: shusenzheng@zju.edu.cn (S.-S. Zheng). |
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Abstract Background: Ischemia reperfusion injury (IRI) causes postoperative complications and influences the outcome of the patients undergoing liver surgery and transplantation. Postconditioning (PostC) is a known manual conditioning to decrease the hepatic IRI. Here we aimed to optimize the applicable PostC 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), PostC group (OLT followed by clamping and re-opening the portal vein for different time intervals, n=20). PostC 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 PostC 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 PostC algorithm. Most of ERS related genes were down-regulated by PostC (10 s×6), especially ATF4, Casp12, hspa4, ATF6 and ELF2, while p-Akt was up-regulated.
Conclusions: PostC 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.
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2018, Vol. 17 
