Study Of The Therapeutic Effect Of Spantide On The Intestinal Originated Infection Of Pancreas In Acute Necrotizing Pancreatitis

Objective: To investigate the expression of substance P in the rats' intestinal tissue and evaluate its effect on the intestinal originated infection of pancreas in acute necrotizing pancreatitis (ANP). And the effect of Spantide, neurokinin-1 receptor (NK-1R) antagonist on the intestinal originated infection was then studied. Methods: 110 adult Sprague-Dawley rats were randomly divided into control group (n=20) and experimental group (n=90): experimental group included 3 subgroups: ANP/NS group (n=30), ANP/Substance P (SP) group (n=30) and ANP/Spantide group (n=30). The rats in control group received laparotomy only. And the rats in experimental group were induced by the retrograde intraductal infusion of 5% sodium taurocholate (1ml/kg). After induction of ANP, normal saline (0.9%NS, 0.5ml) was infused intravenously in ANP/NS group, Substance P (0.0025%, 0.5ml) was infused intravenously in ANP/Substance P group and Spantide (0.0025%, 0.5ml) was infused intravenously in ANP/Spantide group. Sacrifices were made 8h or 16h later in control group and experimental groups after induction respectively, except for survival times of 10 rats in each ANP group were observed. Intestinal mucosal permeability was studied by intrajejunal injection of 100uCi radioactive isotope 99mTechnetium Diethlene Triamine Pentacetic Acid (99m Tc-DTPA) and the radioactivities of 99m Tc-DTPA content in urinary were measured 8h or 6h after induction. The pancreas and intestine were harvested for pathology. The severity of ANP was determined by pathological examination. Immunohistochemistry was used to evaluate the expression and localization of Substance P. Pancreas, mesenteric lymph nodes and the content of ileum were obtained for bacteriological culture.Results: ⑴ In the ANP/NS and ANP/SP group, histological damages in intestinal mucosa and pancreas were observed at 8h after induction, and the damages deteriorated at 16h after induction, and their histology scores were significantly higher than those in the control group (P <0.05). As to the ANP/Spantide group, the histological damages of intestine and pancreas were improved (P <0.05). ⑵The radioactivity of 99m Tc-DTPA in urinary increased significantly in ANP/NS and ANP/SP groups than those of the control group (P <0.05). But the radioactivity of 99m Tc-DTPA in urinary in ANP/Spantide group were lower than these two experimental groups and there were no statistical significance between ANP/NS and ANP/SP groups (P <0.05). ⑶Immunohistochemistry revealed Substance P was expressed mainly on the surface of mucosa,glandular cell and nerve terminal in the intestine of control group, but in experimental groups, it still could be found on inflammtary cells,vessel wall (especially vascular endothelial cell) and some fibroblast in the interstitial. Furthermore, the expression of substance P in the intestine in ANP/NS group increased significantly than that of control group (P <0.05). ⑷ Compared with the control and ANP/Spantide group respectively, bacterial translocations to pancreas and mesenteric lymph nodes in group ANP/NS and group ANP/SP increased significantly (P <0.05). And the most common organism was Escherichia coli. ⑸The mortality of ANP/ Spantide group was significantly lower than that of group ANP/NS and group ANP/SP (P <0.05, respectively). Conclusion: The expression of the substance P and the permeability in the rats' intestine were increased significantly in ANP. And the application of Spantide can protect mucous barrier, decrease the bacterial translocation and reduce the rats' mortality.