| BackgroundAcute pancreatitis (AP) is a potentially fatal disease, which mostly self-limited pancreatitis, but there are still 10% to 20% of patients progressed to severe acute pancreatitis (SAP). SAP is the contemporary difficulties of pancreatic disease, because of its rapid onset, severe condition, rapid progression,and the acute complications often appear early. In recent years, treatment and monitoring of SAP has made some progress, but the mortality remains as high as 20% to 40%.AP cause liver and kidney damage would not only increase the AP condition, but also directly affect the prognosis, even lead to the liver, kidney failure and death. In a retrospective study in SAP with multiple organ dysfunction failure, the highest mortality in patients was liver failure (83%); the mortality of acute renal failure in patients was as high as 45~50% ; and in joint organ failure, the liver and kidney failure mortality is the highest, reaching 91%. Therefore, the study of the treatment of SAP with liver and kidney injure has aroused general interest.In the pathogenesis of SAP, "the release of inflammatory mediators'theory" is aroused general attention. The neutrophils over-stimulated by the phagocytes cells, which leads to release the cytokines and inflammatory medium. The cytokines and inflammatory medium lead to different levels of systemic inflammatory response. Further more, it leads to multiple organ dysfunction syndromes (MODS). The present study showed that the tumor necrosis factor (TNF-a) is the most important inflammatory cytokines in SAP.TNF-a is the most important inflammatory cytokine in SAP .It is involved in induction of IL-1p,IL-6,IL 8 . TNF-a stimulating various inflammatory cells, which release the cytokines and inflammatory mediators out of control. Thus cause pancreatic tissue necrosis, endothelial injury and vascular permeability, leading to organ microcirculation and tissue damage ,even failure.There are numerous studies around the SAP related liver, kidney injury. In these studies, the tumor necrosis factor (TNF-a) are playing an important role. It can direct damage the liver cells and renal tubular, release several cytokines and facilitate the systemic inflammatory response syndrome (SIRS) and liver, kidney injure.In 2001, Bhatic M first proposed the new idea—AP "therapeutic window". There is a"therapeutic window"between AP attack and organ failure for anti-inflammatory. The use of inflammation targeted therapy may reverse MODS events.Studies have shown that use the TNF-a antibody early can improve the SAP's survival rate from 15% to 85% in 72h, and the hyperamylasemia, pancreatic hemorrhage and fat necrosis. were significantly reduce.The pre-experiment suggests: retrograde injected 4.5% NaTc to establish SAP and MODS animal model. The liver and kidney dysfunction peak and the TNF-αreaction peak are 6 hours after establishment of the animal model.Infliximab is a recombination chimerical TNF-a in the sub-types of immune globulin G1 monoclonal antibodies. In this study, we use the single/combined Infliximab and Octretide to observe the experimental effect ion of the liver and kidney damage in the ANP and MODS model. Method40 female SD rats were randomly divided into control group, ANP model group, Infliximab treated group, Octretide treatd group, and Infliximab+Octretide treated group (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, only turning the pancreas, duodenum after the abdomen was closed. Treated group was injected Infliximab or Octretide via caudal vein passage followed by continuous intravenous transfusion by micro-infusion pump in anti-inflammatory media therapeutic window.The rats of each group were observed and sacrificed at 24h after the models were induced. Serum AMS level, TNF-a, serum ALT, serum TB, Cr of rats were determined. Tissue samples of pancreas were prepared for morphological observation under conventional light microscopy, and pathological change of pancreas. Tissue samples of liver and kidney were observed generally, made by light and electron microscopy biopsy. Specificity observed by two pathologists by light microscopy sections, according to the pathological scoring rate. Specific electron microscopy by two teachers observed in liver and kidney ultra structure.Results1,The treated group compared with the ANP model group:(1) Liver and kidney function and serum AMS, TNF-a, the pathological scores of pancreas: the AMS, TNF-a, ALT, TB, Cr, and pancreas pathology score in the treated groups were significantly lower (P<0.05) than the ANP model group.(2) Liver and kidney pathology change and pathology score: the lesion damage was mild in the treated groups by observation in general, light and electron microscope. The pathological score in the treated groups were significantly lower (P<0.05) than the ANP model group.2,Comparison among the treated groups:(1) Liver and kidney function and serum AMS, TNF-a, the pathological scores of pancreas: A,The AMS, TNF-a, ALT, TB, Cr, and pancreas pathology score in the Infliximab+Octretide treated group were significantly lower (P<0.05) than the Infliximab treated group and the Octretide treated group. B,Serum AMS in all treated groups showed no significant difference(P>0.05).(2) Liver and kidney pathology change and pathology score: A,There were similar lesions of gross specimen observation in the three treated groups. B,The lesion damage was mild in the Infliximab+Octretide treated groups by observation in general, light and electron microscope. C,The pathological score in the Infliximab+Octretide treated groups were significantly lower (P<0.05) than the Infliximab group and the Octretide group.Conclusion1, The early use of Infliximab can significantly reduce the TNF-a level in ANP complicating MODS model, and has significant effects in liver and kidney injure.2, Infliximab + Octreotide can significantly increase the efficacy of Infliximab to liver and kidney injure in ANP complicating MODS model. |
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