解放军医学杂志2017，Vol.42Issue(11)：974-978,5.DOI:10.11855/j.issn.0577-7402.2017.11.07
细胞凋亡在重症急性胰腺炎并发急性肺损伤中的作用机制
Action mechanism of apoptosis in the development of acute lung injury after severe acute pancreatitis
摘要
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.关键词
细胞凋亡/重症急性胰腺炎/急性肺损伤/信号转导Key words
apoptosis/severe acute pancreatitis/acute lung injury/signal transduction分类
医药卫生引用本文复制引用
石占利,孙静,李志会,任丹红,章佳颖,方堃..细胞凋亡在重症急性胰腺炎并发急性肺损伤中的作用机制[J].解放军医学杂志,2017,42(11):974-978,5.基金项目
浙江省自然科学基金(LY13H290008) （LY13H290008）
浙江省医药卫生科技计划项目(2011KYB075)This work was supported by the Natural Science Foundation of Zhejiang Province (LY13H290008),and Zhejiang Medical and Health Technology Program (2011KYB075) （2011KYB075）
