Effect of heme oxygenase-1 over-expression on the survival of rats after reduced-size liver transplantation / 中国组织工程研究

ABSTRACT

BACKGROUND: Heme oxygenase-1 (HO-1) plays an important role on preventing tissues and organs from oxidant stress injury, which remains currently one of the most active areas of investigation. OBJECTIVE: To study HO-1 over-expression on the survival and fiver function of rats after reduced-size liver transplantation by constructing recombinant adenovims Ad5-HO-1.DESIGN, TIME AND SETTING: Randomized controlled animal study was performed in the Institute of Pediatrics, Children Hospital Affiliated to Chongqing Medical University from September 2003 to March 2005. MATERIALS: Seventy-four SD rats were used to establish in situ reduced-sized liver transplantation models. METHODS: Recombinant adenoviral vector encoding Ha-1 gene (AdS-HO-1) was generatred by molecular biology method, wluch was administered to donors via voln at 48 hours before transplantation. All rats were randomly divided into control group(n=12),saline group(n=12), cobalt protoporphyrin (CoPP)group(n=13),Ad5-HO-1 group(n=13),Ad5-green fluorescent protein(GFP)group(n=12),and Ad5-HO-1+zinc protoporphyrin (ZnPP)group (n=12).Livers of donor wefe harvested and stored for 24 hours at 4℃ in HTK solution. Before it is implantedinto recipient. MA IN OUTCOME MEASURES: Survival rate and liver function; portal vein blood flow monitored 2 hours after transplantation by Color Doppler How Imaging; pathological changes of transplanted liver tissue observed by HE staining;HO-1 activity, tumor necrosis factor-alpha(TNF-α),Bcl-2 and Bax expression detected by immunohistoehemical staining; changes of HO-1,TNF-α,bcl-2 and bax mRNA detected by molecular viewpoint. RESULTS: Survival rate in the Ad5-HO-1 group was significantly higher than that in the saline group at al,7,and 21 days after liver transplantation(P＜0.05).Glutamic pyruvic transaminase decreased in the Ad5-HO-1 group as compared to that in the saline,Ad5-GFP,and Ad5-HO-1+ZnPP groups(P＜0.05);portal venous blood flow significantly increased 2 hours after transplantation(P＜0.05);HO-1 activity also significantly increased(P＜0.05).RT-PCR and immunohistochemical staining showed that HO-1 and bcl-2 expressions increased(P＜0.05),but bax and TNF-αexpressions decreased(P＜0.05).CONCLUSION:Ad5-HO-1 significantly induces high expression of HO-1 increases portal venous blood flow within 2 hours alter liver transplantation, and promotes liver functional recovery so as to prolong survival time of rats after liver transplantion.