• Liver Int. · Jul 2012

    TNF-α neutralization improves experimental hepatopulmonary syndrome in rats.

    • Li Liu, Nan Liu, Zhi Zhao, Jiabao Liu, Yingmei Feng, Huiqing Jiang, and Delan Han.
    • Department of Medicine, Hebei Key Laboratory of Gastroenterology, Second Hospital of Hebei Medical University, Shijiazhuang, China. Li.liu1968@live.com
    • Liver Int. 2012 Jul 1; 32 (6): 1018-26.

    Background/AimTNF-α is increased in hepatopulmonary syndrome (HPS). Pentoxifylline (PTX) mitigated experimental HPS through the inhibition of TNF-α. However, PTX has pleiotropic effects besides the inhibition of TNF-α. This study is to neutralize TNF-α with specific monoclonal antibody to TNF-α (TNF-α McAb) to investigate the effect of TNF-α on HPS.Materials And MethodsHepatopulmonary syndrome was induced by common bile duct ligation (CBDL); controls were sham operated. The endpoints were 1, 2, 3, 4 and 5 weeks after surgery. (99m) Technetium-macroaggregated albumin (Tc-MAA) was to evaluate intrapulmonary arteriovenous shunts; Portal venous pressure, cardiac output and mean blood pressure (MAP) were also measured. Serum was for Alanine transaminase (ALT), endotoxin, TNF-α and nitric oxide (NO) measurements, liver for histology, lung for histology and iNOS, PI3K/Akt expression assay.ResultsPortal vein pressure was significantly elevated and MAP decreased in CBDL rats. Tc-MAA was mainly located in lung and very weak in brain in sham group and mainly in brain of CBDL rats. TNF-α McAb significantly decreased the radioactivity in the brain, reduced cardiac output, increased MAP and systemic vascular resistance (SVR) in CBDL animals. Serum ALT, endotoxin, TNF-α and NO were significantly increased. TNF-α McAb significantly decreased these serum indices in CBDL rats. TNF-α McAb significantly alleviated liver damage, decreased alveolar-arterial gradient and inhibited iNOS, PI3K/Akt and p-Akt expression in lung tissue. Furthermore, TNF-α McAb significantly attenuated the inflammatory response in lung.ConclusionTNF-α McAb improves HPS in cirrhotic rats; this effect is likely mediated through the inhibition of TNF-α PI3K/Akt-NO pathway.© 2012 John Wiley & Sons A/S.

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