title: Protective effect of eNOS overexpression against ischemia/reperfusion injury in small-for-size liver transplantation.
abstract: Ischemia/reperfusion (I/R) injury can occur during small-for-size liver transplantation, resulting in delayed graft function and decreased long-term graft survival. The aim of the present study was to evaluate the effects of genetic overexpression of endothelial nitric oxide synthase (eNOS) in protecting hepatocytes against I/R injury in a rat model of small-for-size liver transplantation. L02 liver cells were transfected with the eNOS gene using an adenovirus (Ad-eNOS). eNOS expression was detected using quantitative polymerase chain reaction and western blot analysis. To evaluate the effect of eNOS overexpression, L02 cells were placed in a hypoxic environment for 12 h and immediately transferred to an oxygen-enriched atmosphere. Forin vivotesting, rats pretreated with Ad-eNOS or control underwent small-for-size liver transplantation. At 6 h after reperfusion, the bile quantity, serum transaminase and nitric oxide (NO) levels, and histological outcomes were evaluated. Cell apoptosis was assessed by flow cytometry or TUNEL assay.In vitro, Ad-eNOS prevented apoptosis in L02 cells with an increase in the level of NO in culture supernatant.In vivo, Ad-eNOS pre-treatment significantly increased bile production, improved abnormal transaminase levels, diminished apoptosis among liver cells, and decreased hepatocellular damage at 6 h after I/R injury. The eNOS-mediated renal protective effects might be associated with the downregulation of tumor necrosis factor-α and a reduction in macrophage activation in the early stage of reperfusion in small-for-size liver allografts. eNOS-derived NO production significantly attenuates hepatic I/R injury. Thus, eNOS overexpression constitutes a promising therapeutic approach to prevent liver I/R injury following small-for-size liver transplantation.
authors.affiliation: Department of General Surgery, Zhangjiagang Hospital Affiliated to Soochow University, Zhangjiagang, Jiangsu 215600, P.R. China.
authors.forename: Bo
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Department of General Surgery, Zhangjiagang Hospital Affiliated to Soochow University, Zhangjiagang, Jiangsu 215600, P.R. China.
authors.forename: Qiu-Hua
authors.initials: QH
authors.lastname: Liu
authors.affiliation: Department of General Surgery, Zhangjiagang Hospital Affiliated to Soochow University, Zhangjiagang, Jiangsu 215600, P.R. China.
authors.forename: Cui-Jie
authors.initials: CJ
authors.lastname: Zhou
authors.affiliation: Institute of Hepatopancreatobiliary Surgery, Yichang Central People's Hospital, China Three Gorges University, Yichang, Hubei 443003, P.R. China.
authors.forename: Ming-Zheng
authors.initials: MZ
authors.lastname: Hu
authors.affiliation: Department of General Surgery, Zhangjiagang Hospital Affiliated to Soochow University, Zhangjiagang, Jiangsu 215600, P.R. China.
authors.forename: Hai-Xin
authors.initials: HX
authors.lastname: Qian
keywords: ischemia reperfusion injury; liver transplantation; nitric oxide; nitric oxide synthase