Therapeutic Role Of Infliximab On The Intestinal Mucosal Barrier Injury Of ANP Rats Complicating MODS

Background and objectiveSevere acute pancretitis(SAP) is one of the severe diseases with rapid development in clinical, of which the mortality rate is up to 20%-40%[1]. In recent years, studys on the pathogenesis of SAP have shown that SAP is a systematic inflammatory process.In this process TNF-αplays the role of origination that arouses a cascade-like reaction of Inflammatory mediators and cytokines[3] and causes systematic inflammation response syndrome(SIRS). Intestinal mucosa cells are damaged by ischemia, hypoxia, intra- abdominal hypertension and inflammatory mediators, bacterial and toxic translocation through the damaged intestine barrier result in infection of pancreas and multiple organ dysfunction syndrome(MODS), which means"the second hit"and leads to death in final[4-5,46]. Infliximab as a mouse/human chimeric monoclonal antibody of TNF-αcould alleviate the cascade-like reaction by decrease TNF-α[47-48], and somatostatin could inhibit the release of trypsin and inflammatory mediators such as TNF-α,IL-1β,IL-12 and IL-6[22-24]. Thus the use in combination of infliximab and octreotide may decrease the intestine barrier functional disturbance and show cooperative inhibition in secondary SIRS, MODS and sepsis. Currently there have been few studys for therapy of infliximab in ANP and have been lack of reports of using infliximab and octreotide in combination on ANP intestine barrier functional disturbance. Our previous investigation has shown that the time 6 h after induction of ANP model is the peak of TNF-a in ANP complicating MODS model, which could be the anti-inflammatory media therapeutic window[25]. Based on this, our study compared the therapeutic effect of Infliximab or/and Octreotide on ANP rats model complicating MODS on the index of intra- abdominal pressure, intestinal motility , intestinal pathology and concentration of DAO and D-lactate. For the first time, to investigate the improvement on intestine barrier functional disturbance IBFD of ANP rats model complicating MODS with early use of Infliximab or/and Octreotide in anti- inflammatory media therapeutic window and to provide the evidence for clinical research in future.Method40 SD female rats were randomly divided into control group(D), ANP model group(ANP), octreotide treated group(O), Infliximab treated group(A) and infliximab plus octreotide treated group(L) (n=8 respectively). The Aho's method was adopted and improved. ANP animal model was induced by retrograde injection into rat's biliopancreatic duct with 4.5% of NaTc solution. In control group, just ruffled the pancreas and duodenum and then shut the abdomen. In the anti-inflammatory mediator therapeutic window(6h after successful modeling) , octreotide treated group(O), Infliximab treated group(A) and infliximab plus octreotide treated group(L) were injected relatively with Infliximab or octreotide or both via caudal vein passage followed by continuous intravenous transfusion through micro-infusion pump,all the rats were observed and sacrificed 24h after successful modeling. Intra-abdominal pressure, serum amylase level, TNF-a, DAO, D-lactate were detected. Tissue samples of pancreas and ileum were prepared for morphological observation under conventional light microscopy.Results①The contents of Serum amylase, TNF-a and pancreatic pathology score of the octreotide treated group(O), Infliximab treated group(A) and infliximab plus octreotide treated group(L) were obviously decreased (P<0.05) than group ANP. Among the three treated groups , the above parameters of group I and group L were lower than group ANP, and which of group L was lowest. There was a significant difference(P<0.05)②The Small intestine motional rate of the treated groups were higher than group ANP, and the Intra- abdominal pressure, concentration of DAO and D-lactate, intestinal pathology score of the treated groups were lower than those of group ANP in significant differences (P<0.05). The above parameters of group A and group I had no difference (P>0.05), but which of group L were lowest with significant statistically difference compared to group A and I(P<0.05).Conclusions①Early use of infliximab could significantly decrease the content of TNF-a and the Intra-abdominal pressure, relieve inflammation of pancreas and improve the intestinal motility, alleviate intestine barrier functional disturbance.②Infliximab used in combination with octreotide could get better effect in decreasing the Intra- abdominal pressure, improving the intestinal motility and alleviating intestine barrier functional disturbance of rats model with ANP complicating MODS than infliximab or octreotide only.