TNF-α expression induced by NF-κB in pulmonary intravascular macrophages of rats with hepatopulmo-nary syndrome and the effect of pyrrolidine dithiocarbamate on the expression

Abstract

Objective To study the expression of both nuclear factor-κB(NF-κB)and tumor necrosis fac-tor-α(TNF-α)in pulmonary intravascular macrophages(PIM)of rats with hepatopulmonary syndrome (HPS)and the effect of pyrrolidine dithiocarbamate(PDTC)on their expression.Methods The Sprague-Dawley(SD)rats were randomly divided into four groups:control,control+PDTC1CCl4,CCl4+PDTC groups.Arterial blood was collected for measurement of blood gas.Venous blood was sampled for hepatic function and endotoxin level.The mesenteric lymph nodes were dissected for bacteriology studies.Proteins of NF-κB and TNF-a of lung tissue were examined by immunohistochemistry.The activity of NF-κB in lung tissues was measured using electrophoretic mobility shift assay (EMSA).By real-time polymerase chain reaction (PCB)using SYBR Green I,the mRNA expression of TNF-α in lung tissues were detected.Results CCl4 group developed HPS with decreased PaO2 and PaCO2,increased alveolar-arterial oxygen difference(A-aDO2),abnormal hepatic function and increased endotoxin level.Culture-positive mes-enteric lymph nodes were found in 62.5%(5/8)of CCl4,group and 66.7%(6/9)of CCl4+PDTC group(P>0.05 J.All lungs from CCl4 and CCl4+PDTC group showed no accumulation of larse mononuclear macrophagelike cells within the lumen of numerous small muscular and nonnulscular pulmonary vessels.The percentages of vessels with more than 1O adherent macrophages was 60.8%(292/480)in CCl4 group but only 19.6%(106/540)in CCl4+PDTC group(P<0.01).The protein expression of NF-κB and TNF-α Was localized to PIM in CCl4 group.The NF-κB activity and mRNA expression of TNF-α in CCl4 group was significantly higher than that in control,con-trol+PDTC group and CCl4+PDTC group(P<0.05).Conclusion The TNF-α expression in PIM induced by NF-κB play an important role in HPS.The inhibitor of NF-κB PDTC can repress PIM activation and decrease the ex-pression of TNF-α.As result.HPS severity is reduced. Key words: Hepatopulmonary syndrome; Pulmonary intravascular macrophages; Nuclear factor-κB; Tumor necrosis factor-α