2. Academic Validation
  3. Pretreatment Donors after Circulatory Death with Simvastatin Alleviates Liver Ischemia Reperfusion Injury through a KLF2-Dependent Mechanism in Rat

Pretreatment Donors after Circulatory Death with Simvastatin Alleviates Liver Ischemia Reperfusion Injury through a KLF2-Dependent Mechanism in Rat

  • Oxid Med Cell Longev. 2017;2017:3861914. doi: 10.1155/2017/3861914.
Zhongzhong Liu 1,  Xingjian Zhang 1,  Qi Xiao 2,  Shaojun Ye 1,  Chin-Hui Lai 1,  Jun Luo 1,  Xiaoying Huang 1,  Wei Wang 1,  Cheng Zeng 1,  Zibiao Zhong 1,  Xiaoli Fan 1,  Zhiping Xia 1,  Yan Xiong 1,  Xinfang Mao 3,  Qifa Ye 1 2,  Yanfeng Wang 1
Affiliations

Affiliations

  • 1 Zhongnan Hospital of Wuhan University, Institute of Hepatobiliary Diseases of Wuhan University, Transplant Center of Wuhan University, Hubei Key Laboratory of Medical Technology on Transplantation, Wuhan, Hubei 430071, China.
  • 2 Research Center of National Health Ministry on Transplantation Medicine Engineering and Technology, The 3rd Xiangya Hospital of Central South University, Changsha, Hunan 410013, China.
  • 3 Xinjiang Key Laboratory of Biological Resources and Genetic Engineering, College of Life Science and Technology, Xinjiang University, Urumqi, Xinjiang 830046, China.
PMID: 29348789 DOI: 10.1155/2017/3861914
Abstract

Objective: Severe hepatic ischemia reperfusion injury (IRI) can result in poor short- and long-term graft outcome after transplantation. The way to improve the viability of livers from donors after circulatory death (DCD) is currently limited. The aim of the present study was to explore the protective effect of simvastatin on DCD livers and investigate the underlying mechanism.

Methods: 24 male rats randomly received simvastatin or its vehicle. 30 min later, rat livers were exposed to warm ischemia in situ for 30 min. Livers were removed and cold-stored in UW solution for 24 h, subsequently reperfused for 60 min with an isolated perfused rat liver system. Liver injury was evaluated during and after warm reperfusion.

Results: Pretreatment of DCD donors with simvastatin significantly decreased IRI liver Enzyme release, increased bile output and ATP, and ameliorated hepatic pathological changes. Simvastatin maintained the expression of KLF2 and its protective target genes (eNOS, TM, and HO-1), reduced oxidative stress, inhibited innate immune responses and inflammation, and increased the expression of Bcl-2/Bax to suppress hepatocyte Apoptosis compared to DCD control group.

Conclusion: Pretreatment of DCD donors with simvastatin improves DCD livers' functional recovery probably through a KLF2-dependent mechanism. These data suggest that simvastatin may provide a potential benefit for clinical DCD liver transplantation.

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