OBJECTIVETo investigate the molecular mechanism of tumor necrosis factor-alpha (TNF-a) monoclonal antibody (McAb) in hepatopulmonary syndrome using a rat model.

METHODSSixty adult male Sprague-Dawley rats, weighing 250 ± 25 g, were randomized to a sham operation group, a common bile duct ligation (CBDL) group, or a CBDL+TNF-alphat McAb treatment group. The CBDL operation group was further divided into five subgroups, and the CBDL+TNF-alpha McAb treatment group was further divided into four subgroups. After the experimental period, all rats were sacrificed for excision of lung and liver tissues. Hematoxylin-eosin (HE) and Masson staining were performed to observe the extent of liver fibrosis,and HE staining was used to histopathologically assess changes in the lung tissue. Immunohistochemistry and western blotting were used to investigate the changes in expression levels of FAK, p-FAK and PTEN in lung.

RESULTSThe extent of inflammatory responses and fibrosis in the liver was significantly lower in the CBDL+TNF-alpha McAb treatment group as compared to those in the CBDL group. The inflammatory responses in the lung were also significantly lower in the CBDL+TNF-alpha McAb treatment group as compared to that in the CBDL group. The CBDL+TNF-alpha McAb treatment group also showed less extensive distribution of FAK and p-FAK protein in lung tissues,but more extensive distribution of PTEN protein.

CONCLUSIONFAK and PTEN are associated with hepatopulmonary syndrome in rats. The therapeutic effect of TNF-alpha McAb may involve modulation of the expression of FAK and PTEN.