Induction of heme oxygenase-1 by hemin protects lung against orthotopic autologous liver transplantation-induced acute lung injury in rats

Journal of Translational Medicine

Research

Jun Cai¹  Weifeng Yao¹  Xinjin Chi¹  Wanling Gao¹  Ziqing Hei¹  Na Guo¹  Yi Jin² 

[1] Department of Anesthesiology, Third Affiliated Hospital, Sun Yat-sen University, 510630, Guangzhou, Guangdong, China;Department of Pathology, Third Affiliated Hospital, Sun Yat-sen University, 510630, Guangzhou, Guangdong, China;

关键词: Heme oxygenase-1;    Acute lung injury;    Inflammation;    Oxidative stress;    Orthotopic autologous liver transplantation;   

DOI  :  10.1186/s12967-016-0793-0

 received in 2015-07-18, accepted in 2016-01-20,  发布年份 2016

来源: Springer

【 摘 要 】

BackgroundPost-liver transplantation acute lung injury (ALI) severely affects patients’ survival, whereas the mechanism is unclear and effective therapy is lacking. The authors postulated that reperfusion-induced increased oxidative stress plays a critical role in mediating post-liver transplantation ALI and that induction of heme oxgenase-1 (HO-1), an enzyme with anti-oxidative stress properties, can confer effective protection of lung against ALI.MethodsMale Sprague–Dawley rats underwent autologous orthotopic liver transplantation (OALT) in the absence or presence of treatments with the selective HO-1 inducer (Hemin) or HO-1 inhibitor (ZnPP). Lung tissues were collected at 8 h after OALT, pathological scores and lung water content were evaluated; survival rate of rats was analyzed; protein expression of HO-1 was determined by western blotting, and nuclear translocation of Nuclear factor erythroid 2-related factor 2 (Nrf2) and nuclear factor(NF)-κB p65 were detected by Immunofluorescence staining. The inflammatory cytokines and oxidative indexes of lung tissue were determined.ResultsIn lungs harvested at the early stage i.e. 8 h after OALT, Hemin treatment significantly increased superoxide dismutase activities, and reduced malondialdehyde, hydrogen peroxide, interleukin-6, myeloperoxidase, and tumor necrosis factor-α production,which were associated with increased HO-1 protein expression and lower pathological scores and increased survival rate of rats. The underline mechanisms might associate with activation of Nrf2 and inhibition of NF-κB p65 nuclear translocation. However, these changes were aggravated by ZnPP.ConclusionsHemin pretreatment, by enhancing HO-1 induction, increased lung antioxidant capacity and reduced inflammatory stress,protected the lung from OALT-induced ALI at early stage of reperfusion.

【 授权许可】

CC BY   
© Chi et al. 2016