脓毒症大鼠多器官白介素18表达及其与内毒素血症的关系

目的　观察盲肠结扎穿孔术 (CLP)所致脓毒症大鼠重要脏器白介素 18(IL 18)基因表达的变化规律 ,并初步探讨IL 18与内毒素血症的关系。方法　5 4只Wistar大鼠随机分为正常对照组 (n =6 )、CLP组 (n =36 )和重组杀菌 /通透性增加蛋白 (rBPI2 1)治疗组 (n =12 ) ,检测动物肝、肺、肾组织中IL 18mRNA表达水平、内毒素水平和器官功能指标的改变。结果　CLP大鼠肝、肺组织内毒素水平迅速升高 ,于 2h达峰值 (P <0 0 1) ,4 8～ 72h又再度回升 ;肾组织内毒素水平升高较晚 ,于 12h达峰值 (P <0 0 1)。rBPI2 1治疗后各组织内毒素水平均显著降低 (P <0 0 5或 0 0 1)。CLP术后各组织中IL 18mRNA表达显著升高 ,分别于 6～ 12h达峰值 (P <0 0 5 ) ,其后下降。rBPI2 1治疗可显著抑制CLP术后 12h大鼠肺、肾组织IL 18mRNA表达 (P <0 0 5 ) ,肝脏IL 18mRNA表达也降至正常范围。此外 ,与CLP组相比 ,rBPI2 1治疗动物血清谷丙转氨酶、肌酐水平和肺组织髓过氧化物酶活性均显著降低。结论　严重腹腔感染后大鼠体内IL 18mRNA表达明显上调 ,其改变与内毒素的刺激作用密切相关 ;IL 18作为一种重要的促炎细胞因子参与了脓毒症的发生、发展过程。

Interleukin-18 mRNA expression in vital organs in septic rats and its relation to endotoxemia

Objective To observe the change in interleukin-18 (IL-18) mRNA expression in cecal ligation and puncture (CLP) induced sepsis, and to investigate its potential role in the pathogenesis of endotoxemia. Methods Fifty-four Wistar rats were randomly divided into normal group (n=6), CLP group (n=36) and recombinant bactericidal/permeability increasing protein (rBPI 21) treatment group (n=12). Tissue samples from the liver, lungs and kidneys were collected to determine IL-18 mRNA expression. Meanwhile, tissue endotoxin level and the indexes of organ function were also measured. Results After CLP, endotoxin levels in the liver,lungs and kidneys were significantly increased, peaking at 2-12h (P<0.01), then returned to the baseline at 24h. However, 48-72h after CLP, the levels of endotoxin in the liver and lungs were elevated again. IL-18 mRNA expressions in the liver, lungs and kidneys were markedly up-regulated at 6-12h after CLP (P<0.05), followed by declination. Treatment with rBPI 21 could effectively reduce endotoxin levels in the liver, lungs and kidneys (P<0.05 or 0.01). Also, expressions of IL-18 mRNA in the lungs and kidneys were significantly inhibited in rBPI 21-treated animals (P<0.05), and IL-18 mRNA expression in the liver tended to return to the normal range 12h later. In addition, rBPI 21 treatment could effectively improve the function of the liver, lungs and kidneys, as manifested by significant lowering of serum alanine aminotransferase, creatinine levels and pulmonary myeloperosidase activity compared to those without rBPI 21 treatment. Conclusions CLP can markedly up-regulate the expression of IL-18 mRNA in vital tissues, which appears to be associated with CLP-induced endotoxemia. IL-18, acting as an important proinflammatory cytokine, may be involved in the pathogenesis of sepsis resulting in subsequent multiple organ dysfunction.