急性坏死性胰腺炎继发感染的防治研究

Intervention strategies for secondary infection following acute necrotizing pancreatitis in rats

  • 摘要: 目的:观察不同措施对大鼠急性坏死性胰腺炎(ANP)继发内毒素和细菌移位的防治效果。方法:Wistar大鼠随机分为正常对照组和6个治疗组,观察胰腺病理、肠上皮细胞间紧密连接、血淀粉酶、内毒素、TNF-α、IL-1β、肠通透性、肠道菌群、脏器细菌移位率和死亡率的变化。结果:中药清胰汤和SDD的效果最好,中药在抑制胰酶分泌和维护肠通透性方面略胜一筹,而SDD则在改善菌群结构方面更具优势;两者在减轻内毒素和细菌移位上效果相当。单纯导泻效果令人失望。生长抑素从多方面显示出其有益的作用,但主要发挥于ANP的早期。两种细胞因子拮抗剂在一定程度上减轻ANP的病情。结论:中药清胰汤、SDD、生长抑素是防治ANP继发感染的有效措施。免疫干预有潜在的应用前景。

     

    Abstract: Objective: To observe the effects of 6 intervention measures on gut barrier function and endotoxin bacterial translocation (BT) following acute necrotizing pancreatitis (ANP) in rats. Methods: A lethal model of ANP was reproduced by infusion of artificial bile into biliopancreatic duct and then divided randomly into: (1) ANP group (n=39, no treatment),(2) Chinese medicine group (n=9), (3) MgSO 4 group (n=6), (4) SDD group (n=8), (5) somatostatin group (n=19), (6)TNFα McAb group (n=6) and (7) IL-1ra group (n=6). Blood levels of amylase, D lactic acid, TNFα, IL-1β and endotoxin were measured, intestinal flora and incidence of BT to organs were examined, and morphology of pancreas and tight junction on ileum epithelia was assessed on cryofracture replicas at various time points. Results: In early stage of ANP, flora disturbance and tight junction damage occurred in the gut, plasma D lactate and endotoxin levels were increased, and BT rate was as high as 59.5% at 72 h. Serum TNFα and IL-1β were elevated significantly. Treatment with Chinese medicine markedly improved gut barrier function and reduced BT rate (37%), blood levels of amylase, endotoxin and cytokines. Having similar purgative response as Chinese medicine, MgSO4 did not show any beneficial effect on gut barrier protection, and the incidence of endotoxemia and BT was not reduced. In SDD group, flora balance was preserved well, and similar results as Chinese medicine were obtained. Somatostatin markedly blunted amylase and cytokine release and ameliorated gut barrier damage during early phase of ANP. TNFα McAb and IL-1ra also alleviated pathologic changes in pancreas and endotoxemia. Conclusion: Treatment with Chinese medicine, SDD and somatostatin attenuated gut barrier damage and BT after ANP, and could be advisable for reducing the chance of secondary infection after ANP, while purgation alone was not effective.

     

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