The Experimental Study Of Intervention Mechanism Of Gabexate Mesilate And Penehyclidine Hydrochloride To Mesenteric Microcirculation In Severe Acute Pancreatitis

Objective: SAP (Severe Acute Pancreatitis), which with high rate of death is a hazardous disease, and the pathogenesy haven't been revealed. Since the pancreatinum-self-digest theory was raised by Chliari in 1896, other theories such as the second attack, which leaded by waterfallover-potency inflammatory factors, the dysfunction of pancreatic microcirculation, the cell apoptosis, low-calciumemia, gut bacteria translocation, et al, were also raised. These theories supplement the knowledge of SAP. The research lay on the microcirculation and gene is the focus of basic and clinical study. This research induce SAP model by injecting 5% sodium tanrocholate to pancreatic duct retrograded, and select Gabexate Mesilate and Penehyclidine Hydrochloride as intervention. The aim is to study the pathogenesy of SAP from microcirculation, explore intervention mechanism of Gabexate Mesilate and Penehyclidine Hydrochloride to mesenteric microcirculation in Severe Acute Pancreatitis, and offer experimental evidence to clinical treatment.Methods: 160 healthy SD rats, which weight 330±30g, were randomly divided into 20 groups (with 8 in every one): sham operation (SO) 2h 6h 12h 24h group, SAP (SAP) 2h 6h 12h 24h group, Gabexate Mesilate treated (GM) 2h 6h 12h 24h group, Penehyclidine Hydrochloride treated (PH) 2h 6h 12h 24h groups, Gabexate Mesilate associate Penehyclidine Hydrochloride treated (PH+GM) 2h 6h 12h 24h groups. The SAP group induced by injecting 5% sodium tanrocholate to pancreatic duct, and use the jugular vein intubate give normal saline and drug. SO group don't inject sodium tanrocholate, only push pancreas. Every treat group gives drug in set time. The ascites amount and general change of organ were observed. The morphous of mesenteric microcirculation: the distinctness of micrangium, the veinule and micrangium caliber were observed. The fluid state of veinule: blood flow rate, fluid state, agglutination were detected. The peripheral vessels state changes of veinule: haemorrhage, exudation were detected. The changes of AMY, LIP, ET, NO, pathologic grade of pancreas and ileum were detected.Results: 1 Comparison with SO group, the ascites amount, the general change of organ, the AMY,LIP,NO,ET, ET/NO level, the pancreas and ileum pathologic change in B group increased significantly. The distinctness, caliber and blood flow rate of veinule and micrangium, the mucosal thickness, the villus height in SAP group decreased significantly (P<0.01). 2 Compared with SAP group, the general change of organ, ascites amount, AMY, LIP, NO, ET, ET/NO level in GM, PH, PH+GM group decreased significantly (P<0.01), the distinctness, caliber and blood flow rate of veinule and micrangium, the villus height, mucosal thickness increased significantly (P<0.01). 3 The microcirculation of PH group improved greater than GM group(P<0.05), while the enzymology change in GM group increase much more. 4.Compared with GM, PH group, the general change and pathologic score of pancreatic and ileum, ascites amount, AMY, LIP, NO, ET, ET/NO level in PH+GM group decreased significantly (P<0.05), the distinctness, caliber and blood flow rate of veinule and micrangium, the villus height, mucosal thickness increased significantly (P<0.05 or P<0.01).Conclusions: 1 Intragraded injecting of 5% sodium tauro- cholate to pancreatic duct can induce SAP with mesenteric microcirculation dysfunction model, this is a duplicated, valuable and reliable method. 2 In SAP, there are lots of ascites and saponify blots of organ, obvious mesenteric microcirculation dysfunction and pathologic changes of pancreas and ileum. As the time prolong, the conditions become worse. It indicates that there is obvious microcirculation dysfunction in mesenteric and other organ. 3 In SAP, as the increase of NO, ET of plasma, the mesenteric microcirculation dysfunction aggravate. It indicates that NO and ET are the important factors that contribute to the microcirculation dysfunction. 4 The associate use of GM and PH can decrease the amount of ascites and saponify blots of organ and pathologic changes of pancreas and ileum. 5 The associate use of GM and PH can decrease the levels of AMY, LIP in serum and NO, ET in plasma, improve the mesenteric microcirculation. 6 The associate use of GM and PH can improve the mesenteric microcirculation,decrease the pathologic changes of pancreas and lessen the condition of SAP.