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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 investigate the effect and significance of oxymatrine (OMT) on serum TNF-α, IL-1β, IL-6 and IL-10 in serum and pancreatic tissue of rats with acute necrotizing pancreatitis (ANP). METHODS: A total of 120 standard Wistar rats were randomly divided into 3 groups: sham operation group (SO group), ANP group and ANP+OMT group. Rat model of acute necrotizing pancreatitis was replicated with sodium taurocholate. The OMT administration method was intraperitoneal injection of sodium taurocholate in the pancreatic duct for 15 minutes after intraperitoneal injection of 50 mg·kg-1.h-1 for 3 times. The levels of endotoxin (ET), TNF-α, IL-1β, IL-6 and IL-10 in serum and pancreatic tissue of the same group at different time (4, 8, 12 and 16 h) and at the same time were observed. At the same time, the pathological changes of pancreatic tissue, 24h mortality and mean survival time of rats in each group were observed. Results: ET, TNF-α, IL-1β, IL-6 and IL-10 in serum and pancreatic tissue at 4, 8, 12 and 16 h in ANP group and ANP+OMT group (in addition to 16 h in ANP group IL-10) All of them were significantly higher than SO group (P<0.01-0.05), and ET, TNF-α, IL-1β and IL-6 in ANP group and ANP+OMT group increased with progression of disease (P<0.05); ANP group IL The level of -10 decreased with progression of the disease (P<0.05). The level of IL-10 in the ANP+OMT group increased with the progression of the disease (P<0.05). At the same time period except for ET in ANP group and ANP+OMT group, there was no significant difference (P>0.05). The levels of TNF-α, IL-1β and IL-6 in ANP group were significantly higher than those in ANP+OMT group (P<0.01). The level of IL-10 in the ANP+OMP group (excluding the 4h group) was significantly higher than that in the ANP group (P<0.01 to 0.05). There was no significant difference in the pathological changes of pancreatic tissue between ANP group and ANP+OMT group, but the 24-hour mortality of ANP+OMT group was significantly lower than that of ANP group (P<0.05). The average survival time was significantly longer than that of ANP group (P< 0.05). Conclusion: OMT can reduce the production of pro-inflammatory cytokines TNF-α, IL-1β and IL-6, upregulate the negative regulation of anti-inflammatory cytokine IL-10, and help reduce the inflammatory cytokine cascade like ANP. The reaction reduced the 24h mortality rate of rats and prolonged the average survival time.