The Experimental Study Of Damage Of Gut Barrier And Intervention Of Pentoxifylline And Gabexate Mesilate In Severe Acute Pancreatitis

Objective: Severe Acute Pancreatitis (SAP) is a severe acute abdomen of surgery, which often episodes emergency and is often succumb to secondum multiple organ failure (MOF). The near research shows that gut is the central and initial organ of MOF, and the mechanisms and interventions of damage of gut barrier is one of the focuses of nearest research. The pentoxifylline (PTX), which has the characteristicses of theobromine, caffeine and theophylline, is a xanthine derivative. The Gabexate Mesilate (GM) is an artifical chemosynthesis drug, which belongs to proteinase inhibitors of non-peptide-kind. Now, the GM was mainly used in the therapy of acute edematous pancreatitis, and the PTX also been used in the therapy of chronic pancreatitis, while the reports on the usage of PTX in SAP wasn't seen. So this research induce SAP with gut barrier damage model by injecting 5% sodium tanrocholate to pancreatic duct retrograded, and observe the mucosal thickness, the height of villus, the microcirculation change of mucous membrane. The AMY, LIP levels of serum and the LPS, TXB2 and 6-keto-PGF1αlevels of plasma were detected. The effectiveness of PTX, GM to the gut barrier was studied. The aim is to reveal the damage mechanisms of gut barrier, find effective intervention and experimental evidence to clinical treatment.Methods: 160 healthy SD rats were randomly divided into 20 groups: sham operation 2h 6h 12h 24h groups, SAP 2h 6h 12h 24h groups, PTX treated 2h 6h 12h 24h groups, GM treated 2h 6h 12h 24h groups, PTX+GM treated 2h 6h 12h 24h groups. SAP with gut barrier damage model was induced by retrograde injection of 5% sodium tanrocholate to pancreatic duct and set up administration by external jugular vein. The administration quantity based on the time and weight. The general changes of the organ and the microcirculation change of mucous membrane were observed on time. The mucosal thickness, the villus height and the pancrase pathologic score according to desires were detected. The endotoxin, 6-keto-PGF1α, TXB2, AMY, LIP detecting method were based on the kit description.Results:1 Compare with SO group, SAP group has lots of ascites, There are obviously edema, hemorrhage, necrosis, saponify blots in pancrase, and obviously thickening, anabrosis, congestion in the gut which has lost luster. The AMY, LIP, LPS level elevate significantly (P<0.01). The mucosal thickness, the villus height decreased (P<0.01), while the pancrase pathologic score were increased significantly (P<0.01).2 Except at SAP6h, the diameter of microvessels and blood flow rate of other groups of SAP decreased significantly, the TXB2, 6-keto-PGF1α, TXB2/6-keto-PGF1αalso increased as the time extend.3 The edema, hemorrhage necrosis in pancrase, the anabrosis and congestions in gut were obviously decreased respectively in PTX, GM, PTX+GM groups. Compared with propotional SAP group, in every treatment groups the AMY, LIP and LPS level decreased significantly (P<0.01), the mucosal thickness, the height of villus increased(P<0.01), the diameter of microvessels and blood flow rate increased(P<0.01). The TXB2, 6-keto-PGF1α, TXB2/6-keto-PGF1αalso decreased as the time extend (P<0.05 or P<0.01).4 Comparison with PTX or GM group, in PTX+GM group, the AMY, LIP, LPS level of plasma decreased significantly(P<0.05 or P<0.01), the mucosal thickness, the villus height increased(P<0.05 or P<0.01), the diameter of microvessels and blood flow rate increased(P<0.05 or P<0.01), the TXB2, 6-keto-PGF1α, TXB2/6-keto-PGF1αalso decreased (P<0.05 or P<0.01).Conclusions:1 Intragraded injecting of 5% sodium taurocholate to pancreatic duct can induce SAP with gut barrier damage model, this is a duplicated, valuable and reliable method.2 In SAP, there are obvious pathologic changes on intestinal mucosa, also, the level of LPS of plasma increase significantly, and as the time prolong, the conditions become worse. It indicates that there is damage of gut barrier in SAP.3 In SAP, there is disturbance on microcirculation of intestinal mucosa, and the more disturbances, the more damage of intestinal mucosa and LPS level gets. It indicates that it is the disturbance of microcirculation leads to the damage of gut barrier.4 In SAP, the TXB2 level and TXB2/6-keto-PGF1αincrease, the disturbance of microcirculation and pathologic changes of intestinal mucosa become aggravated, the LPS level increase. It indicates that the TXB2 and 6-keto-PGF1αare the important factors of the disturbance of microcirculation.5 After the intervention of PTX and GM, they all can lessen the inflammatory reaction of pancreas, and thereby lessen the influence to other organ. The combine effect of PTX and GM is much better.6 After the intervention of PTX and GM, the TXB2 level and TXB2/6-keto-PGF1αdecrease, the disturbance of microcirculat- ion and pathologic changes of intestinal mucosa become lessened, the LPS level also decrease. It indicates that PTX and GM have the protection to gut barrier, and the combine effect of PTX and GM is much better than solo-use of PTX or GM.