奥曲肽对急性坏死性胰腺炎炎症介质的调节作用

Effects of octreotide on the changes of pro-inflammatory mediators in experimental acute necrotizing pancreatitis

目的 观察奥曲肽对急性坏死性胰腺炎 (ANP)大鼠肿瘤坏死因子α(TNFα)、一氧化氮(NO)和内毒素等炎症介质的影响 ,并探讨其对ANP大鼠的治疗作用。方法 SD大鼠 93只 ,随机分为 3组 :ANP生理盐水处理组 (ANP +NS组 )、ANP奥曲肽治疗组 (ANP +奥曲肽组 )和假手术组 (SO组 )。观察各组大鼠的平均存活时间和存活率、血清淀粉酶活性、腹水量、胰腺系数及病理形态变化 ;测定血浆内毒素、血清TNFα及血清NO2 -/NO3 -的含量 ,测定胰腺组织一氧化氮合酶 (NOS)的活性变化 ,并应用还原辅酶Ⅱ黄递酶组织化学方法显示胰腺组织NOS的表达及其分布。结果 奥曲肽治疗组大鼠平均存活时间及存活率均显著高于ANP +NS组 (P <0 0 5 ) ;血清淀粉酶活性、腹水量、胰腺系数、血浆内毒素、血清TNFα和NO2 -/NO3 -水平均明显低于ANP组 +NS组 (P <0 0 5 ) ;胰腺组织NOS含量较ANP +NS组显著降低 ;胰腺组织血管内皮细胞和导管上皮细胞NOS表达较ANP +NS组显著下降 ;胰腺组织病理学改变减轻。结论 奥曲肽对ANP大鼠有肯定的治疗作用 ,其机制可能与其对内毒素、TNFα和NO等炎症介质的调节作用有关。

Objective To evaluate the effects of octreotide on the changes of pro inflammatory mediators, such as tumor necrosis factor α (TNFα), nitric oxide (NO) and endotoxin in acute necrotizing pancreatitis (ANP) of rats and its therapeutic action Methods Male SD rats were assigned to three groups: ANP treated with octreotide (ANP+octreotide), ANP treated with normal saline(ANP+NS), and sham operation(SO) The survival rate and mean survival period of rats were noted Serum amylase activity, ascites volume, pancreatic index, plasma endotoxin level, serum TNFα concentration and NO 2 -/NO 3 - level were determined at 3h, 6h, 12h after operation Nitric oxide synthetase (NOS) activity and expression in pancreas were also observed Results Mean survival period and survival rate of rats were higher in ANP+octreotide group than these in ANP+NS group( P <0 05) Serum amylase activity, ascites volume, pancreatic index, plasma endotoxin and serum TNFα concentration were significantly lower in octreotide treated group than these in ANP+NS group at all the indicated time points 12 hours after induction of ANP, both serum NO 2 -/NO 3 - concentration and NOS activity in pancreatic tissue were increased; expression of NOS in pancreatic tissue was also enhanced Octreotide could lower both serum NO 2 -/NO 3 - concentration and NOS activity in pancreatic tissue and down regulate the expression of NOS Pathological study showed pancreatic hemorrhage and necrosis were alleviated and fine structure of pancreatic acinar cells were preserved in octreotide treated group Conclusion This study indicated that octreotide has definite therapeutic effect on experimental ANP The possible mechanisms were related to its inhibition on over production of TNFα, NO and endotoxin, and down regulation on NOS over expression in pancreatic tissue