Preliminary Study Of The Animal Model Of Acute Pancreatitis And Associated Lung Injury Mechanisms

Acute pancreatitis(AP) is an acute pancreatic inflammation made by blocks of pancreatic duct with sudden intraductal hypertension and ins- ufficient blood. It performs autodigestive process resulting in pancreatic and systemic reactions after trypsin is activated. Its morbidity is about 40/100000, only less than acute appenditis's, small intestine obstruction's, cholecystitis's and gastroduodenal ulcer's. About 80% of acute pancreatitis is mild in symptom with little complication and no death occurring. The other 20% will develop pancreatic necrosis resulting in systemic inflammation reaction syndrome [SIRS] with high mortality of some 40% .The deaths will occur in the first week after the attack, sharing 60% of total mortality and mostly associated with respiratory failure. Because of the lack of its pathophysiogenesis, it is necessary to strengthen researches for clinical services. On the basis of the animal model induced by intraductal administration of 1.0%, 2.0%, 3.5% sodium taurocholate, TNF-a, ICAM-l, NOS in the pancreas and the lung were detected by immunohistochemistry during development of AP from mild type to severe type. The effects of above-mentioned factors in the pathophysiogenesis of AP were investigated in order to provide the testing foundation to the diagnosis, treatment and prevention of this disease. The main results and conclusions are as follows: 1. AP was successfully induced in Winstar rats by sodium taurocholate. The observation results of postoperative living animal, edematous severity of the pancreas and the lung tissues, the enzymic level of sera and ascites, along with general optical microscopic and electro-microscopic examination shows that the model is similar to clinical AP and to be a good one with which the molecular mechanism of the disease is researched. 2. The expression of TNF-c was not found in the normal pancreas and lung tissues. The over expression of TNF-a gradually raised along with the aggregation of macrophages in accordance with the severity of inflammation. These results indicated that TNF-cw was a key mediator in the inflammatory reaction. 3. No constitutive or low-level expression of ICAM-1 was found in the normal pancreas tissue. The over expression of ICAM- 1 gradually raised gradually with the severity of inflammation and endothelial injury. These results indicated that the reaction between ICAM-1 and TNF-c~ could induce leukocyte coherence and infiltration resulting in vasco-endothium and tissue injury and plasm outflow. Over expression of ICAM-lonly in the lung tissue of the necrosis and haemorrhagic pancreatitis shows ICAM-l is an important cytokine resulting in injury of distant organs. 4. Constitutive or low-level expression of NOS was not found in the normal pancreas and the lung tissues. The over expression of NOS raised gradually in accordance with the severity of inflammation and endothelial injury. These results indicated that the NOS would play a two-side role in modulation of micro-circulation during inflammation process. (Figure 1) 5. Electro-microscopic examination showed the destroy of vasco- endothelial architecture and the abruption of intracellular junction in pancreas and lung. These results implied that they were the morphological basis of the associated lung injury in AP.