氧化苦参碱对急性坏死性胰腺炎大鼠血清和胰腺组织中炎性介质的影响

The role of oxymatrine on serum and pancreas tissue changes of TNF-α,IL-1β, IL-6 and IL-10 in rats with acute necrotizing pancreatitis

目的:探讨氧化苦参碱(OMT)对急性坏死性胰腺炎(ANP)大鼠血清和胰腺组织中TNF-α、IL-1β、IL-6和IL-10含量的影响及其意义。方法:选择标准Wistar大鼠120只,随机分为3组:假手术组(SO组)、ANP组和ANP+OMT组,以牛磺胆酸钠复制急性坏死性胰腺炎大鼠模型。OMT用药方法为胰管内给予牛磺胆酸钠后15min腹腔内注射给药50mg·kg-1.h-1,共3次。动态观察同组不同时间(4、8、12、16h)及不同组同时间的血清和胰腺组织中内毒素(ET)、TNF-α、IL-1β、IL-6和IL-10含量变化,同时观察各组大鼠胰腺组织的病理变化、大鼠24h病死率及平均生存时间。结果:ANP组和ANP+OMT组在4、8、12和16h的血清和胰腺组织中ET、TNF-α、IL-1β、IL-6和IL-10(ANP组IL-10除16h外)均显著高于SO组(P<0.01～0.05),且ANP组和ANP+OMT组ET、TNF-α、IL-1β和IL-6随病程进展而升高(P<0.05);ANP组IL-10水平随病程进展降低(P<0.05),ANP+OMT组IL-10水平随病程进展增高(P<0.05)。在相同时段除ET在ANP组和ANP+OMT组差异无统计学意义外(P>0.05),ANP组TNF-α、IL-1β和IL-6水平显著高于ANP+OMT组(P<0.01),而ANP+OMP组IL-10水平(除4h组外)显著高于ANP组(P<0.01～0.05)。ANP组和ANP+OMT组大鼠胰腺组织的病理变化无明显差异,但ANP+OMT组大鼠24h病死率显著低于ANP组(P<0.05),平均生存时间较ANP组显著延长(P<0.05)。结论:OMT可减少促炎细胞因子TNF-α、IL-1β和IL-6的产生,上调抗炎细胞因子IL-10的负调控作用,有助于减轻ANP时炎性细胞因子瀑布样级联反应,降低大鼠24h病死率,延长平均生存时间。

Objective： To explore the role of oxymatrine （OMT） on serum and pancreas tissue changes of TNF-α, IL-1β, IL-6 and IL-10 in rats with acute necrotizing pancreatitis（ANP）. Methods： One hundred and twenty wistar rats were randomly divided into 3 groups： Sham operation group（SO）, ANP group and ANP＋OMT group（ANP＋OMT）. The ANP model was established by using retrograde injection of sodium taurocholate into cholangiopancreatic duct. In ANP＋OMT group, OMT （50 mg · kg^-1· h^-1 × 3） was injected intravenously 15 rain after injecting sodium taurocholate. The changes of serum and pancreas tissue ET, TNF-α, IL-1β, IL-6 and IL-10 in iso-group aniso-time and aniso-group iso-time were observed. Meantime the pathological study was performed as well. Results： The levels of serum and pancreas tissue ET, TNF-α, IL-1β, IL-6 and IL-10 （except 16h IL-10 of ANP group） in rats of ANP and ANP＋OMT group were significantly higher than those of SO （P 〈0.01-0.05）. The levels of ET, TNF-α, IL-1β and IL-6 were significantly increased in iso-group aniso-time （P 〈0.05）, but the levels of IL-10 were signifi- cantly decreased in aniso-time of ANP group and significantly increased in aniso-time of ANP＋OMT group （P 〈0.05）. Although the levels of ET had not significant difference between ANP and ANP＋OMT groups, the levels of TNF-α, IL-1β and IL-6 of ANP group were significantly higher than those of ANP＋OMT group （P 〈0.01） and the levels of IL-10 of ANP＋OMT group （except 4 h group） were significantly higher than those of ANP group （P 〈0.01）. The pathological change of ANP and ANP＋OMT groups had not signifi- cant difference, but the 24 h fatality rates and average survival time of group ANP＋OMT were obvious higher than those of group ANP （P 〈0.05）. Conclusion： OMT could decrease the production of TNF-α, IL-1β and IL-6 and up-regulated the anti-inflammation effect of IL-10, which could relieve cytokines cascade reaction, decrease the 24 h fatality rates and improve average survival time of rats with ANP.