The Effect Of Aminoguanidine And Tienam On The Bacterial Translocation In Mice With Severe Acute Pancreatitis

Background:The severe acute pancreatitis is very dangerous, and it developes very rapidly, and always involves multi-organs. Because of lacking specific treatment, the complications and mortality are still on a high level. SAP can be divided into acute reaction period(in two weeks),systemic infection period(two weeks to two months and above) and residual infection period(complication during advanced stage and sequelae period, most happen after two months).The improvement of combined therapies make a lot of patients survive the acute reaction period. But during the systemic infection period, the MODS happening is the main cause of death. It has been reported that the pancreas and ambipancreas getting infection in SAP is high to 40%～70%,and if complicate sepsis, the mortality will over 20%～50%.So it is very important to prevent bacterial translocation during SAP treatment. The current view is that the pathogenic bacteria which infect the necrosis pancreas and the ambipancreas mainly come from the intestinal tract. Deitch thought that the bacteria translocates from the intestinal tract after the intestine suffered three attacks. The first attack was probably the ischemia and hypoxia. The second attack was the returning of the blood flow in intestines, followed the neutrophilic leukocyte translocating to the intestinal microcirculation, and releasing ctyokone. The ischemia-reperfusion could even damage GALT and enterocyte. The third attack was the loss of integrity of the intestinal barrier. It permitted the toxic substance and the bacteria permeating the intestinal wall. The mechanism of the bacterial translocation mainly includes :1.the loss of the physical barrier of the intestinal mucosa;2.immune function suppressing;3.the stepping down of the enterokinesia;4.the imbalance of the intestinal bacteria. The route of the bacterial translocation is still unclear, maybe they translocate into the ectointestinal tissue by the lymphatic vessel or the blood, etc. The iNOS is activated in SAP, and produce lots of NO. The massive NO destroys intestinal mucosa. Such as long-term exposure to the NO disorders the intestinal cell's paracrine secretion or the autocrine function;suppress cell's breath;bad-distribute the regional blood flow;overproduce the oxidative peroxynitrite. Above-mentioned routes cause the intestinal damage, intestinal barrier function disorder, and bacterial translocation in result. In addition the NO produced by the iNOS can destroy the pancreatic microcirculation, cause ischemia,necrosis. The pancreatic infection is in relationship with the pancreatic necrosis. Necrosis seldom occurs in tissue which is not necrosis. Inhibiting iNOS activation and prophylactic antibiotics can prevent the bacterial translocation availably in theory. This experiment studied the influence of the selective iNOS suppression aminoguanidine and tienam on the bacteria infection of the tissue which out of the intestine by establishing the animal model of the SAP, and explored the influence of them on the bacterial translocation and the possible pathway of the bacterial translocation, and provided more vigorous rationale and basis to the clinic therapy.Methods:①The experimental animals were randomly divided into normal group,SAP group,SAP plus aminoguanidine group,SAP plus tienam group and SAP plus aminoguanidine plus tienam group;②The animal model of SAP was induced by the intrapancreatic injections of 5% sodium taurocholate with a dosage of 2.5ml/kg.Intervened the model by aminoguanidine and tienam.Collecting samples after 48 hours.③The SAP model was assessed by the serum amylase and the pancreatic histopathologic change under the light microscope;④Assessed the intestinal mucosa damage by the appearance under the light mocroscope;⑤Detected the pancreatic MPO by chemical chromatometry;⑥Detected the D-lactic acid by enzymological spectrophotometry;⑦Carried out the bacterial culture on portal vein blood,pancreas,MLN,liver,ascite.Results:①By serology detection and histology observation we confirmed that the model accords to the diagnostic criteria of SAP;②The level of pancreatic MPO in SAP group was obviously higher than the normal group (P<0.05),while the level was obviously lower than SAP group in SAP plus aminoguanidine group,SAP plus tienam group,SAP plus aminoguanidine plus tienam group(P<0.05);③The serum D-lactic acid level in SAP group and SAP plus tienam group was predominantly higher than the normal group's (P<0.05).But there was no statistical distinction between SAP group and the SAP plus tienam group (P>0.05). While the level was obviously lower in SAP plus aminoguanidine group,SAP plus aminoguanidine plus tienam group than SAP group and SAP plus tienam group(P<0.05).④There were no bacterial growth in normal group's organs by bacterial culture. Every organs cultured bacteria in SAP group, and among of them the ascetic positive rate was the highest, second was the pancreas, then was the MLN, the liver and the blood's positive rate were lowest. The positive rate was lower in SAP plus aminoguanidine group,SAP plus tienam group and SAP plus aminoguanidine plus tienam group. But the ascetic rate was still the highest.The positive bacterium were all intestinal bacteria, most was E coli, next was aerobacter cloacae,enterococcus faecalis,proteus mirabilis,enterococcus faecalis.Conclusions:(1)aminoguanidine could protest the enteromucosa, prevented the increase of the intestinal permeability and prevented the intestinal bacteria permeating the enteromucosa to suppress the bacterial translocation and declined the pancreatic infection rate;(2)tienam prevented the pancreatic infection by suppressing the intestinal bacterial translocation. But tienam couldn't release the enteromucosa's damage, and it was useless to the improvement of the enteromucosa's permeation;(3)the bacteria infecting the pancreas was from the intestine in SAP.