首页|期刊导航|中华医学杂志(英文版)|Effects of heme oxygenase-1 on pulmonary function and structure in rats with liver cirrhosis
中华医学杂志(英文版)2011,Vol.124Issue(6):918-922,5.DOI:10.3760/cma.j.issn.0366-6999.2011.06.021
Effects of heme oxygenase-1 on pulmonary function and structure in rats with liver cirrhosis
Effects of heme oxygenase-1 on pulmonary function and structure in rats with liver cirrhosis
摘要
Abstract
Background The hepatopulmonary syndrome (HPS) is a severe vascular complication in lungs resulting in systemic hypoxemia in patients with cirrhosis and portal hypertension. The underlying structural change in HPS is intrapulmonary vasodilation, which can lead to impaired oxygenation of pulmonary venous blood. It has been demonstrated that the heme oxygenase-1/carbon monoxide (HO-1/CO) system plays an important role in the control of vascular tone. The aim of this study was to further investigate the role of HO-1 in the pathogenesis of HPS in animal model.Methods Totally 35 rats were divided into liver cirrhosis, zinc protoporphyrin Ⅸ (ZnPP), cobalt protoporphyrin (CoPP)and sham groups. Biliary cirrhosis was established in the first three groups by bile duct ligation. Rats in the ZnPP and CoPP groups received once intraperitoneal injection of ZnPP and CoPP, respectively, 24 hours before sample collection.Expression of HO-1 mRNA in lung was detected by reverse-transcription polymerase chain reaction, while protein expression was determined by immunohistochemical analysis. Hematoxylin and eosin staining was performed to confirm the presence of liver cirrhosis and intrapulmonary vasodilation. Arterial blood gases, mean arterial pressure and portal vein pressure were also measured. Analysis of variance or Wilcoxon statistical methods were used to determine statistical significance.Results Compared with the sham group, the cirrhotic group demonstrated increased expression of pulmonary HO-1 mRNA and protein (P<0.01). The level of arterial carboxyhemoglobin (COHb), alveolar-arterial oxygen gradient (A-aPO2),mean arterial pressure, portal vein pressure (P<0.05, respectively), and intrapulmonary vasodilation were also significantly increased. Compared with the cirrhotic group, CoPP treatment increased pulmonary HO-1 mRNA and protein expression, the level of A-aPO2 (P <0.05 respectively), COHb (P <0.01), and intrapulmonary vasodilation, while ZnPP treatment decreased pulmonary HO-1 mRNA and protein expression, the level of COHb (P <0.05 respectively),and intrapulmonary vasodilation, without obvious alteration of mean arterial pressure and portal vein pressure.Conclusion Increased pulmonary HO-1 expression is an important contributor to the development of experimental HPS.关键词
heme oxygenase-1/carbon monoxide/hepatopulmonary syndrome/fibrosisKey words
heme oxygenase-1/carbon monoxide/hepatopulmonary syndrome/fibrosis引用本文复制引用
GUO Shi-bin,DUAN Zhi-jun,LI Qing,SUN Xiao-yu..Effects of heme oxygenase-1 on pulmonary function and structure in rats with liver cirrhosis[J].中华医学杂志(英文版),2011,124(6):918-922,5.基金项目
This study was supported by grants from the National Natural Science Foundation of China (No.30970886) and the Science and Technology Project of Dalian (No.2008E13SF193). (No.30970886)