The expression of tumor necrosis factor receptor-1 and caveolin-1 in the lung of acute pancreatitisassociated lung injury rats and the therapeutic role of Qingyitang

Abstract

Objective To investigate the expression and function of tumor necrosis factor receptor-1 (TNFR-1) and caveolin-1 (Cav-1) in the lung of acute pancreatitis-associated lung injury rats, and to determine the potential role of Qingyitang. Methods Wistar rats were randomly divided into sham operation (SHAM) group, acute lung injury (ALI) group, dexamethasone (DEX) group and Qingyitang (QYT)group. ALI was induced by retrograde injection of deoxycholate into biliopancreatic duct of rats. Blood and lung tissues were drawn after 24 h. Serum amylase, lung wet/dry (W/D) ratio and pathological section were examined to evaluate the degree of lung injury. Immunoradioassay was used to detect serum tumor necrosis factor-α (TNF-α). Reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting were applied to detect the expression levels of TNFR-1 and Cav-1 mRNA and protein respectively. Results The concentration of serum amylase, the W/D ratio, TNF-α (4.82 ± 0.14 vs 2.96 ± 0. 30, P ＜0. 01 ) and the degree of pathological lung injury were obviously increased in ALI rats. The expression of TNFR-1 mRNA was increased in ALI rats (1.29 ±0. 15 vs 0.43 ±0.05,P＜0.01), but Cav-1 mRNA expression was decreased ( 1.14 ±0. 10 vs 2.00 ±0. 10,P ＜0.01 ). The expression of TNFR-1 protein in both lipid rafts and non-lipid rafts was increased, but that of Cav-1 in both of the two fractions was decreased. As compared with ALI rats, the concentration of serum amylase, W/D ratio, TNF-αt ( DEX: 3.79 ± 0. 11,QYT: 3.66 ±0. 10, ALI: 4.82 ±0. 14,P ＜0.01 ) and the degree of pathological lung injury were obviously decreased in DEX and QYT rats. The expression of TNFR-1 mRNA was decreased in both DEX and QYT groups (DEX: 0.48±0.01, QYT: 0.49 ±0.02, ALI: 1.29 ±0. 15,P＜0.01), but that of Cav-1 mRNA was up-regulated (DEX: 1.66 ±0.06, QYT: 1.52 ±0.04, ALI: 1.14 ±0. 10,P＜0.01). The expression of TNFR-1 protein in both lipid rafts and non-lipid rafts was decreased, but that of Cav-1 protein was increased.Conclusion The up-regulated expression of TNF-α/TNFR-1 and the down-regulated expression of Cav-1 suggest that both of them may play an important role in acute pancreatitis-associated lung injury. DEX and QYT may relieve lung injury effectively by regulating the expression of TNFR-1 and Cav-1. Key words: Acute pancreatitis;  Acute lung injury;  TNFR-1;  Caveolin-1