急性坏死性胰腺炎肺组织炎性介质mRNA表达与肺损伤的关系

Intrapulmonary gene expression of inflammatory mediators in rats with acute necrotizing pancreatitis

目的探讨急性坏死性胰腺炎（ANP）大鼠肺组织白细胞介素6（IL-6）、肿瘤坏死因子-α（TNF—α）及细胞间黏附分子（ICAM-1）等炎性介质mRNA表达与肺损伤的关系。方法33只Wistar大鼠随机分为正常对照和胰腺炎不同时间点（1、4、12和24h）各组，应用3．5％牛磺胆酸钠逆行胰胆管注射制备ANP模型。采用RT—PCR法检测ANP肺组织IL-6、TNF-α及ICAM-1 mRNA表达，同时观察血淀粉酶及脂肪酶、胰腺和肺组织湿／干重比率及病理改变。结果造模ANP 1h 后肺组织IL-6、TNF-α及ICAM-1mRNA水平（1．25±0．16、0．33±0．09及0．82±0．03）较正常对照组（0．07±0．02、0．06±0．02及0．41±0．04）表达增高（P〈0．05），并持续升高至12及24h（分别为1．67±0．14、0．99±0．11、1．17±0．05及1．87±0．05、0．96±0．06、1．11±0．04），同时伴有肺组织病理损害，其严重程度与肺TNF—α及ICAM-1 mRNA表达、肺组织湿／干重比率与TNF-α、IL-6、ICAM—1 mRNA表达的相关系数分别为0．93及0．70（P〈0．05）。结论大鼠ANP早期肺组织IL-6、TNF-α及ICAM-1 mRNA即过度表达，肺IL-6、TNF-α及ICAM-1 mRNA过度表达是ANP肺损害发生的原因之一，肺损伤严重程度与IL-6、TNF—α及ICAM-1 mRNA表达的高低有关。

Objective To investigate intrapulmonary expression of IL-6,TNFα and intercellular adhesion molecule-1 （ICAM-1） mRNA and relationship between the gene expression of inflammatory mediators and lung injury in acute necrotizing pancreatitis （ANP）. Methods ANP was induced with 3.50% sodium taurocholate by the method of retrograde pancreatic-injection. Animals were sacrificed at 1, 4, 12 and 24 hours after induction of pancreatitis. Intrapulmonary IL6, TNF-a and ICAM-1 mRNA expression was assayed by reverse transcription-PCR. The serum amylases and lipases levels, pancreatic and pulmonary wet/dry weight ratio, histologic grading of ANP and lung injury were deter mined. Results Taurocholate pancreatitis showed alveolar septal thickening and leucocyte infiltration in the lung. There was intrapulmonary overexpression of the IL-6, TNF-α and ICAM-1 mRNA at 1 hour and persisted up to 12-24 hours with the increase of serum amylases and lipases levels after induction of pancreatitis. Score of the lung injury was correlated well with expression of TNF-α and ICAM 1 mRNA （r=0.93, P〈0.05）. Pulmonary wet/dry weight ratio was correlated with intrapulmonary expression of the IL-6, TNF-α and ICAM-1 mRNA （r=0.70,P〈0.05）. Conclusion The expression of IL-6, TNFa and ICAM-lmRNA is related to the production of lung injury in ANP. Severity of lung injury can be early assessed by the overexpression of IL-6, TNF-α and ICAM-lmRNA in ANP.