Protective effect of eNOS overexpression against ischemia/reperfusion injury in small-for-size liver transplantation
| Autor: | Cui‑Jie Zhou, Ming‑Zheng Hu, Qiu‑Hua Liu, Hai‑Xin Qian, Bo Zhang |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
Cancer Research
medicine.medical_treatment Liver transplantation Transaminase Nitric oxide Andrology 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Immunology and Microbiology (miscellaneous) Enos nitric oxide medicine ischemia reperfusion injury TUNEL assay biology liver transplantation nitric oxide synthase General Medicine Articles medicine.disease biology.organism_classification Nitric oxide synthase chemistry Apoptosis 030220 oncology & carcinogenesis Cancer research biology.protein 030211 gastroenterology & hepatology Reperfusion injury |
| Zdroj: | Experimental and Therapeutic Medicine |
| ISSN: | 1792-0981 |
| Popis: | 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. For in vivo testing, 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|