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P-4.61 Brain death-mediated inflammatory liver injury is mediated by hepatocytes apoptosis through TRAIL

Zhong-kun Huo, People's Republic of China

The First Affiliated Hospital of Zhengzhou University

Abstract

Brain death-mediated inflammatory liver injury is mediated by hepatocytes apoptosis through TRAIL

Zhong-Kun Huo1,2,3, Dong-Jing Yang1,2,3, Ji-hua Shi1,2,3, Jie Li1,2,3, Wen-Zhi Guo1,2,3, Shui-Jun Zhang1,2,3.

1Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, People's Republic of China; 2Henan Key Laboratory of Digestive Organ Transplantation, Zhengzhou, People's Republic of China; 3Zhengzhou Key Laboratory of Organ Transplantation Technology&Application Engineering, Zhengzhou, People's Republic of China

Background: Brain death-mediated liver injury is the major risk of liver graft dysfunction in liver transplantation. Tumor necrosis factor ligand superfamily member 10(TNFSF10/TRAIL), a cytokine induces cell death, represents a targeted therapy against cancer, mainly through death receptors of TNFSF10 including TNFSF10A and TNFSF10B.In this study, we sought to clarify the role of TNFSF10 in brain death-mediated liver injury.
Method: The brain-dead rat model was established by increasing intracranial pressure in Sprague-Dawley(SD) rats. The livers harvested at after brain death 0h, 1h , 2h, 4h, 6h were then used for further detection and analysis. M1/M2 macrophages were derived from THP-1 cells. LO2 cells were treated with different concentrations of rTRAIL under hypoxia/reoxygenation. The cell survival was measured by CCK-8 assay. TRAIL, Caspase-3, BAX and BCL-2 were examined at levels of gene and protein both in vivo and in vitro.
Results: TRAIL expression followed a pattern that it decreased in total but had a transient increase at 1h after brain death in rats.TRAIL expression was shown in the CD68+INOS positive macrophage (M1 macrophage polarization) in the liver sections from brain-dead rats by IF. rTRAIL can induce cell death by CCK8.TRAIL expression was significantly up-regulated in THP-1 cells after M1 macrophage polarization vs M2 in vitro by RT-PCR(P<0.05).BCL-2 significantly decreased in LO2 cells treated with rTRAIL than without treated under hypoxia/reoxygenation condition (P<0.05), while Caspase-3 and BAX significantly increased in LO2 cells treated with rTRAIL (P<0.05).
Conclusion: TRAIL expression follows a typical transient rise pattern.TRAIL expression significantly up-regulated with M1 polarization of macrophage, which induces apoptosis in hepatocytes, accounting for inflammatory liver injury caused by brain death.

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