The Experimental Study Of The Changes Of Angâ…¡ And Renal Microcirculation And Intervention Of Enalaprilat In Severe Acute Pancreatitis

Objective: Severe Acute Pancreatitis (SAP) is a severe acute abdomen surgery emergency, which often occurs incidently and is often complicated by multiorgan dysfunction syndrome (MODS). The incidence rate of renal dysfunction in SPA patients was only lower than lung functional disturbance in the complicating organs damage besides pancreas and it is often with most other organ system dysfunction and high mortality rate when developing to acute renal failure (ARF) which was one of the most important death reasons in SAP. Therefore, it is very important to prevent renal failure early. The latest research shows that renal microcirculation disturbance is the main reason for renal damage. Enalaprilat is an active metabolite of enalapril maleate in vivo, which could repress angiotensin-converting enzyme. Now, enalaprilat is mainly used for the treatment of acute hypertension. Although enalapril has been reported to be gavaged in SAP, it has not been reported to be used intravenous route in SAP. This study constructed rat model of SAP with renal microcirculation disturbance by injecting 5% sodium tanrocholate to pancreatic duct retrograded and treated the rat SPA models with enalaprilat through intravenous route. Then we observed the hemoperfusion of renal cortex, the caliber of blood capillary, the density change of blood capillary. Meanwhile, we detected the serum amylase, lipidase, angiotoninII and renal function. Through the above experiments we studied the effectiveness of Enalaprilat on microcirculation disturbance in kidney. This study is aim to reveal the damage mechanisms of renal microcirculation disturbance, find the effective intervention and provide experimental evidence to clinical treatment.Methods: seventy-two healthy SD rats were randomly divided into 9 groups: sham operation 2h, 6h and 12h (SO2h, 6h, 12h) groups, SAP 2h, 6h and 12h (SAP2h, 6h, 12h)groups, Enalaprilat treated 2h, 6h and 12h (Ena2h, 6h, 12h) groups. SAP with renal microcirculation disturbance rat model was induced by retrograde injection of 5% sodium tanrocholate to pancreatic duct and set up administration by vena caudalis. The administration quantity based on the time and weight. Observe the general changes of the organ, the microcirculation change of kidney on time. The AMY, LIP, BUN, Cr, AngII levels of serum was detected and the effectiveness of Enalaprilat to the renal microcirculation disturbance was studied. All statistical analyses were carried out with SPSS 12.0.Results:1 Ascites: little and clear ascites in SO groups and a lot of red ascites (3-12ml) in SAP group. The ascites increased with the time (P<0.05). 2 The changes of pathomorphology: we found that pancreas had edema, hyperemia and necrosis in SAP groups. Under microscope we found edema, hyperemia and necrosis in acinus and interstitial of pancreas pancreatic. We also found that the blood was widespread in renal glomerulus and the red cell and epithelial cell cast was also found in renal tubules. With the time longer, the index and renal scores increased significantly, too (P<0.01).3 The serum level of AMY, LIP, BUN and Cr in SAP group all increased significantly (P<0.01).4 The changes of renal microcirculation: The level of hemoperfusion in SAP group increased significantly too (P<0.01).5 The level of AngII of SAP group was stepping higher than that of SO groups (P<0.01).6 The changes in Ena groups6.1 The dose of ascitic decreased significantly in Ena groups (P<0.05);6.2 The changes of pancreas and kidney's pathomorphology.6.2.1 Observation by eyes: we found that the degree of pancreas'edema, hyperemia and necrosis lessened in Ena groups.6.2.2 Observation in light microscope: we found that the degree of pancreas'edema, hyperemia and necrosis lessened in Ena groups,and the pathological changes of kidney lessened too.6.3 The level of AMY, LIP, BUN and Cr in group with treatment decreased significantly among different time points (P<0.05).6.4 The changes of renal microcirculation: The renal cortical blood perfusion had significant difference among the different groups (P<0.05) and it was the same about capillary diameter (P<0.05) and the capillary density (P<0.01).6.5 AngII levels in plasma decreased significantly (P<0.01).Conclusions:1 Intragraded injecting of 5% sodium taurocholate to pancreatic duct can induce SAP with renal microcirculation disturbance model and this is a duplicated, valuable and reliable method.2 In SAP, there are obvious pathologic changes and renal inadequacy on kidney. With the time prolonged, the condition becomes worse. It indicates that there has severe damage of kidney in SAP.3 In SAP, there is disturbance on microcirculation of kidney and the more serious, the more severe pathology damage in kidney and the more severe renal inadequacy level. It is the disturbance of microcirculation that leads to the damage of kidney.4 In SAP, with the AngII level increasing, the microcirculation of nephridial tissue was disorded and the disturbance of microcirculation become aggravated. It shows RAS was acted in SAP and AngII is the important factor of the disturbance of microcirculation.5 After the intervention of Enalaprilat, the microcirculation disturbance of kidney and damage of kidney was lessened, and renal function was improved. It indicates that Enalaprilat has the protection to kidney.