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TNF ‐α neutralization improves experimental hepatopulmonary syndrome in rats
Author(s) -
Liu Li,
Liu Nan,
Zhao Zhi,
Liu Jiabao,
Feng Yingmei,
Jiang Huiqing,
Han Delan
Publication year - 2012
Publication title -
liver international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.873
H-Index - 110
eISSN - 1478-3231
pISSN - 1478-3223
DOI - 10.1111/j.1478-3231.2012.02821.x
Subject(s) - hepatopulmonary syndrome , medicine , tumor necrosis factor alpha , portal venous pressure , protein kinase b , endocrinology , transplantation , liver transplantation , cirrhosis , portal hypertension , chemistry , apoptosis , biochemistry
Background/Aim TNF ‐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 methods Hepatopulmonary 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. Results Portal 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. Conclusion TNF ‐α McAb improves HPS in cirrhotic rats; this effect is likely mediated through the inhibition of TNF ‐α PI 3K/Akt‐ NO pathway.