小剂量胰岛素对脓毒症大鼠急性肺损伤巨噬细胞移动抑制因子和氧化应激的影响

Effects of small dosage insulin on expression of macrophage migration inhibitory factor and degree of oxidative stress in acute lung injuried sepsis rats

目的观察小剂量胰岛素对脓毒症大鼠急性肺损伤巨噬细胞移动抑制因子(MIF)和氧化应激的影响,探讨胰岛素的肺保护作用及其机制。方法 30只雄性SD大鼠随机分为假手术组、脓毒症组、胰岛素治疗组,以盲肠结扎穿孔法建立脓毒症大鼠模型。各组于建模后12 h处死,分别测定动脉血氧分压(PaO2)、肺湿干质量比(W/D)、肺组织匀浆丙二醛(MDA)、总抗氧化能力(T-AOC)测定、肺组织NF-КB/p65及MIF表达水平及肺损伤病理程度等。结果脓毒症组肺W/D、MDA、NF-КB/p65、MIF、MIF mRNA及病理损伤程度较假手术组显著上升(P<0.05),T-AOC和PaO2显著下降(P<0.05);而胰岛素治疗组与脓毒症组比较肺W/D、MDA、NF-КB/p65、MIF、MIF mRNA及病理损伤程度显著下降(P<0.05),T-AOC和PaO2显著上升(P<0.05)。结论小剂量胰岛素能够下调MIF的表达和抑制氧化应激,对脓毒症大鼠急性肺损伤有保护作用,其机制可能与抑制NF-КB活化有关。

To observe the effects and mechanism of small dosage insulin on expression of macrophage migration inhibitory factor and the degree of oxidative stress in acute lung injuried rats.【Methods】 Thirty male Sprague-Dawley（SD） rats were randomly divided into sham operation group,sepsis group and insulin therapy group.Sepsis models were established by cecal ligation and puncture.Rats were killed at 12 h after operation.Blood and lung were obtained for detecting the index of PaO2,lung wet/dry weight ratio（W/D）,level of malondialdehyde（MDA） and total antioxidant capacity（T-AOC） in lung homogenate,NF-КB/p65 were detected by ELISA.MIF mRNA were detected by RT-PCR,and MIF protein was determined by immunohistochemistry,the lung pathological change was observed by light microscope.【Results】W/D,MDA,NF-КB/p65,MIF expression level and pathological injury extent of the lung tissue in sepsis group were significantly increased compared with sham operation group（P 0.05）,while those index were significantly decreased in insulin therapy group（P 0.05）.T-AOC and PaO2 were obviously lower in sepsis group than sham operation group（P 0.05）,but those index were increased in insulin therapy group（P 0.05）.【Conclusions】Small dosage insulin can protect acute lung injuried sepsis rats by down-regulating the expression of MIF and reaction of oxidative stress.The mechanism of the protective effects may be associated with decreased expression of NF-КB.