Action mechanism of apoptosis in the development of acute lung injury after severe acute pancreatitis / 解放军医学杂志

ABSTRACT

Objective To explore the role of apoptosis in the development of acute lung injury (ALI) after severe acute pancreatitis (SAP) and its mechanism via Notch/Hes signal transduction pathway in the pathologic process.Methods Fifty healthy male Sprague Dawley rats were randomly divided into,sham group (n=8) and model group (n=42).Tissue samples of model group were collected randomly at 3 (n=10),6 (n=10),12 (n=10) and 24h (n=12) after model establishment.Tissue collection of Sham group was conducted at 3h.Left lung wet/dry weight ratio (W/D) was calculated;Histological scores of pancreatic and lung tissues were assessed under microscope;myeloperoxidase (MPO) and tumor necrosis factor-α (TNF-α) of lung tissues were determined by enzymatic-chemical method and radioimmunoassay method respectively.Apoptosis of lung cells was evaluated by TUNEL assay followed by calculation of apoptosis index.Protein levels of Notch-l,Hes-1 and Hes-5 were also detected semi-quantitatively by Western blotting.Results The lung tissue W/D of model rats exhibited a gradual increment at the prior 12 hours,and the ratio was significantly higher than that of sham group at each time point (P＜0.01) while it reached the peak at 12h time point.Pancreatic and lung pathological scores of model groups were increased at all time points and significantly higher than sham group (P＜0.01).Lung pathological scores of model groups achieved a peak at 12h.Meanwhile,lung MPO and TNF-α of model groups showed the same increment trend at each time points.The apoptosis index (AI) of lung cells in model groups were higher than that in sham group (P＜0.01).Compared with sham group,the model groups showed lower protein expression levels of Notch-1,especially at 3,6 and 12h (P＜0.05).Notch-1 protein expression level of 12h group was lower than that of 3,6 and 24h groups (P＜0.01).Correlation analysis found that apoptosis of lung cells was significantly negatively related to histopathological scores (r=-0.834,P＜0.01).The Notch-1 protein expression showed positive correlation with AI (r=0.515,P=0.004),but significantly negative correlation with W/D (r=-0.593,P=0.001),histological scores (r=-0.306,P=0.002),MPO (r=-0.687,P＜0.01) and TNF-α (r=-0.574,P=0.001) in the lung tissue.Conclusions Lung cell apoptosis,which is negatively correlated to tissue injury levels,may play an important role in the development of ALI after SAP.Inhibitory state of Notch-1 signaling transduction can aggravate ALI in the pathologic process.