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The Effect Of Triptolide On Activation Of NF-κB In ANP Rats

Posted on:2004-02-23Degree:MasterType:Thesis
Country:ChinaCandidate:W L DiFull Text:PDF
GTID:2144360095450299Subject:General Surgery
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Acute necrotizing pancreatitis (ANP) is one of the common acute clinical abdominal diseases. Because its pathogenesis is unclear, there are no effective measures to treat it, so its mortality is very high. Recent researches show that over-activation of white cell causes a lot of inflammatory mediators releasing. It can cause systemic inflammatory response syndrome (SIRS) and multiple organs dysfunction syndrome (MODS) which is the main reason of death for patients at the early stage of ANP. At present nuclear transcription factor- K B(NF- K B) is considerated the "switch off' of inflammatory reaction. NF- K. B enters into the nuclear when it is activated, then transcribe a lot of inflammatory mediators: TNF- a , IL-1. IL-6, IL-8 and oxygen free radicals which is the main causes of multiple organs damage of ANP. It would be a good way that NF- K B is inhibited by some drugs to treat ANP. The study that triptolide treats ANP by inhibiting activation of NF- K B is few.AimOur research mainly demonstrate:!. Changing of NF- K, B activition have relation with the levels of inflammatory mediators and damage of pancreas , liver and kidney; 2. Does triptolide, the inhibitor of NF- K B, decrease the function and pathological injury in the ANP rat?.MethodsNinty Wistar rats were randomly allocated into three groups: sham operation group (group S). Acute necrotizing pancreatitis group (group A), treatment group withtriptolide (group T). There were 30 rats in each group. Rat ANP model was induced by retrograde injection of 5% sodium taurocholate to pancreatic duct. Triptolide was given by intraperitonel injection 0.2mg/kg,.q12h , 0.05mg/ml. Put rat to death after operation at 2h, 6h,and 12h, determine serum level of AMY, ALT, Cr, TNF- a and IL-6 at three time points (10 rats for every time points). The serum levels of AMY, ALT and Cr were detected with biochemical analyzer; The serum levels of TNF- a and IL-6 were detected with radioimmuno assay. Blood lymphocyte smear and pancreatic tissue were made to detected the activity of NF- K B by immunohistochemistry, and tissues from pancreas, liver and kidney were obtained to odserve the changes with microscope and changes of ultrastructure with electron microscope. All data were analyzed with statistic software SPSS 10.0. Results1. The level of Serum AMYSerum AMY Levels were significantly discriminating at 2, 6, and 12h after operation in three groups. Serum AMY Levels group A and T were higher than those in group S (P<0.05) . Serum AMY Levels were significant difference between group A and T at 12h after operation (P<0.05 ) .2. The levels of TNF- a and IL-6At the three time points, the levels of TNF- a and IL-6 in group A and T significantly increased compared to those in group S with the development of ANP (P<0.05, P<0.05) In group T they significantly decreased compared to those in group A at 3 time points (P<0.05 ) .3. The level of ALTAt 2h, 6h, and 12h after operation, the levels of ALT increased rapidly in group A . They significantly increased compared to those in group S ( P<0.05 ) . Serum ALT levels were significant difference between group A and T at 6 and 12h after operation (P<0.05,P<0.05) . 4 The level of CrThe levels of Cr were less discriminating at 2h and 6h after operation in three groups. At 12h, they have significantly discrimination in three groups. Levels of Crwas higher than those in group S and T (P<0.05, P<0.05)5. Activation of NF- K B in pancreatic tissue and blood lymphocyte Activition of NF- K B in pancreatic tissue and blood lymphocyte were significanthigher at 2h and 6h in group A compared to those in group S and T (P<0.05, P<0.05). While there were no significant difference among 3 groups at 12h after operation (P>0.05) .6. In group S, pancreatic, hepatic and renal tissues were normal under optical microscope. While group A and group T pathological damage was very severe. Pancreatic edema, acinar cell necrosis, haemorrhage, onaceous spot and extensive fat necrosis were...
Keywords/Search Tags:Acute pancreatitis, rat, triptolide, NF-KB
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