瑞芬太尼对腹腔感染脓毒症小鼠肝肺组织诱导型一氧化氮合酶的影响

Effect of remifentanil on iNOS in lung and liver tissue of septic mice

目的观察瑞芬太尼对腹腔感染脓毒症小鼠肺组织和肝组织诱导型一氧化氮合酶（iNOS）的影响。方法采用小鼠盲肠结扎穿孔术制备脓毒症模型，将40只雄性昆明小鼠随机分为假手术组（Sham组）、脓毒症组（CLP组）、瑞芬太尼治疗组（R1组）、瑞芬太尼对照组（R2组）。Western blot方法检测肺组织和肝组织iNOS蛋白表达，双抗体夹心酶联免疫吸附法测定肝肺组织白细胞介素（IL）-10和IL-6水平，观察PaO2、肺组织髓过氧化物酶（MPO）活性、血清ALT和AST活性及电镜下组织超微结构改变。结果与Sham组比较，CLP组PaO2显著降低，肺组织和肝组织中iNOS蛋白表达、肺组织MPO活性、ALT和AST活性显著增强（P〈0．01），肺组织IL-6和IL-10水平显著增加为649．74±90．47和501．06±57．67（P〈0．01），肝组织IL-6和IL-10水平显著增加为341．05±28．73和267．50±41．82，112组以上指标均无明显变化；与CLP组比较，R1组PaO2明显增加，iNOS蛋白表达，IL-6和IL-10水平,MPO活性、ALT和AST活性显著降低（P〈0．01），电镜显示肺组织和肝组织损伤程度较CLP组略减轻。结论瑞芬太尼对脓毒症感染致急性肺损伤和肝损伤有保护作用，其机制可能通过抑制iNOS蛋白的表达，降低炎性因子水平有关。

Objective To investigate the effect of remifentanil on the inducible nitric oxide synthase （iNOS） expression in lung and liver tissue of the septic mice. Methods Forty male KM mice were randomly divided into four groups （ n = 10 in each group） ： sham-operated group （ sham group）, cecal ligation and puncture （CLP） group （CLP group） ,remifentanil treatment group （R1 group） ,and remifentanil control group （ R2 group）. The mouse model of CLP was used to observe arterial partial pressure of oxygen （PaO2 ）, myeloperoxidase activity, ALT and AST activity, the level of IL-6 and IL-10 in lung and liver tissue homogenate. The iNOS protein expression was detected by Western blot. The pathologic changes were observed under an electron microscope. Results Compared with sham group, iNOS protein expression, myeloperoxidase activity,ALT and AST activity,IL-6 and IL-10 （649.74 ± 90.47 and 501.06 ± 57.67 in the lung,341.05 ±28.73 and 267.50 ±41.82 in the liver） levels were markedly increased in CLP group （P 〈 0.01 ）, but PaO2 was significantly reduced （P 〈 0.01 ）. Compared with CLP group, iNOS protein expression ,IL-6 and IL-10 levels, myeloperoxidase activity, and ALT and AST activity in R1 group were significantly decreased （ P 〈 0.01 ）. The pathologic changes induced by sepsis were significantly attenuated by remifentanil under the electron microscopy. Conclusion Remifentanil might have a protective effect against sepsis. Its action mechanisms are probably involved in the inhibition of inflammatory factor production and suppression of iNOS expression.