The Pathogenic Role Of Polymorphonuclear Neutrophil In Acute Lung Injury Caused By Severe Acute Pancreatitis And The Effects Of Qingyitang

Acute lung injury(ALI) is a common complication of severe acute pancreatitis(SAP). It is the consequence of extensive destruction of the lung vascular endothelial cells and alveolar epithelial cells caused by excessive organic inflammatory response. Researchers have studied different kinds of cytokines and inflammatory medium which mediate ALL And now the role of PMN in the mechanism of ALI becomes the hot point. Clinical and experimental studies show that there are a lot of PMNs gathering in the lung in SAP. In physiological function, PMN's survival cycle is short. It maintains mobile balance with apoptosis. Apoptosis is different from necrosis. The important is that apoptotic cells can be removed by phagocytes or other cells without inducing inflammatory response. If the apoposis of PMN is abnormal, the PMNs will gather. That induces PMNs' respiratory burst and toxic contents of PMN will be released to cause tissue damage. Therefore we take great interest in the mechanism of PMN's gathering , the change and the mediator of apoptosis in ALI in SAP. It is assumed that we can inhibit PMNs' gathering , promote PMNs' apoptosis and restrict excessive respiratory burst to protect the lung through controlling the trigger.Basis upon the above investigation, we established rat model of ALI caused by SAP by retrograde injection of 1.5% sodium deoxycholate into the common bile-pancreatic duct. 138 rats were divided into 5 groups at random: sham operation group (SHAM, n=18); models of ALI caused by SAP group (SAP, n=30); SAP+ ulinastatin treated group (ULI, n=30); SAP+ dexamethasone treated group (DEX, n=30);SAP+ Qingyitang treated group (QYT, n=30); Rats were killed at post injection hour 6, 12, 24 respectively. The PMNs in BALF were isolated and examined by flow cytometry, RT-PCR and immunohistochemistry method. The following indexes were dynamicallyobserved: 1) the expression of CD lib/CD 18 on the surface of PMN, ICAM-1 on the surface of lung vascular endothelial cell and alveolar epithelial cell, s-ICAM in serum ; 2) the change of apoptosis of PMN in ALI in SAP and its signal transduction; 3) the change of respiratory burst of PMN; 4) the effect of different drugs on the function of PMN in ALI in SAP. It is to explore the mechanism of ALI caused by SAP and the role of PMN. It is the theoretic basement of new clinical treatment. The experimental results are:1. Establishing the rat model of ALI caused by SAP1.5% sodium deoxycholate was injected inversly into the common bile-pancreatic duct of rats. The model rats appeared accelerated respire and cyanoses. The artery blood gas analysis showed declined PaO2, increased PaCO2 and raised A-aDO2. That indicated the rats had severe hypoxemia. The pathology of lung showed an increase in vascular permeability and pulmonary edema , hemorrhage. A lot of PMNs gathered in the lung. The death rate 24h after injection reached 50%. All of the above suggested the model rats had ALI caused by SAP.2. The role of the expression of ICAM in the gathering of PMNsThe expression of CDllb/CD18 on the surface of PMN in BALF and ICAM-1 in lung tissue in SAP group were stronger than those in SHAM group at all appoint time. The strongest expression were at 12h and 24h after injection respectively. The levels of sICAM-1 in serum in SAP group were higher than those of SHAM group at all appoint time. It reached the peak at 24h after injection. There was positive correlation between the ALI induced by SAP and sICAM-1 in serum. That suggests the level of sICAM-1 in serum can be a sign of ICAM-1 in lung and PMNs' gathering.3. The study of apoptosis of PMNs and its signal transduction in ALI caused bySAPThe apoptosis ratio of PMN in BALF in SAP group was lower than those in SHAM group at all appoint time. It decreased to the minimom at 12h after injection. Inversly, the survival ratio was higher in SAP group than in SHAM group. It means the apoptosis of PMN in BALF was delayed and the survival time of PMN was prolonged. The lung injury was probably related with the delayed apoptosis of PMN fo...