脓毒症大鼠肺损伤时肺组织巨噬细胞移动抑制因子变化及丙酮酸乙酯的干预作用

Change of macrophage migration inhibitory factor mRNA expression and effects of ethyl pyruvate on the lung injury of rats induced by sepsis

目的观察脓毒症大鼠肺损伤时肺组织巨噬细胞移动抑制因子(MIF)mRNA的变化及丙酮酸乙酯(EP)的干预作用。方法雄性Wistar大鼠,以盲肠结扎穿孔法建立脓毒症大鼠模型。80只大鼠随机分为假手术组、脓毒症组、EP早期治疗组(建模后6h给药)和EP晚期治疗组(建模后12h给药)。各组分别于模型建立后24h和48h检测肺组织MIF mRNA、髓过氧化物酶(MPO)的活性、肺湿重/干重(W/D)比以及肺组织的病理变化。结果24h、48h脓毒症组、EP6h组和EP12h组MIF mRNA、MPO活性、肺W/D比值以及肺组织的病理学评分均较假手术组显著升高;EP6h组和EP12h组肺组织MIF mRNA水平、MPO活性、肺W/D比值以及肺组织的病理学评分均较同时相点脓毒症组显著降低;脓毒症组24h肺组织MIF mRNA的水平与MPO、W/D比值以及肺组织病理学评分的变化之间呈显著正相关。结论脓毒症大鼠肺损伤时肺组织MIF mRNA的表达显著升高,EP对脓毒症肺损伤有保护作用,其机制可能与其抑制MIF的表达有关。

Objective To observe the expression of macrophage migration inhibitory factor （MIF） mRNA and the effects of ethyl pyruvate（EP） on the lung injury in sepsis rat. Methods In a sepsis model by cecal ligation and puncture, eighty Wistar male rats were randomly divided into sham operation group, sepsis group, EP 6h treatment group（received EP introperitoneally 6h after CLP） and EP 12h treatment group（received EP introperitoneally 12h af- ter CLP）. Animals were sacrificed at 24 and 48 h after operation. The lung tissue samples were collected to determine the expression of MIF mRNA （by real-time PCR）, pulmonary myeloperoxidase （MPO） activity and wet/dry lung weight ration. The pathological changes in lung tissues were observed with light microscopy after HE staining. Re- suits Compared with sham operation group, the expression of MIF mRNA, the activity of MPO, the ratio of wet/ dry lung weight and the pathological scores of lung injury were markedly elevated in sepsis group and EP treatment group at 24h and 48h after operation. The previous results compared with sepsis group, the expression of MIF mRNA, the activity of MPO, the ratio of wet/dry lung weight and the pathological scores of lung injury were markedly decreased in EP treatment group. The expression of MIF mRNA was correlated with the changes in the ac- tivity of MPO, the ratio of wet/dry lung weight and the pathological scores of lung injury in the sepsis group at 24h after operation. There were no statistic difference between early EP treatment group and late EP treatment group. Conclusion The expression of MIF mRNA obviously increases on the lung injury induced by sepsis. EP could inhibit the expression of MIF mRNA to exert the protective effects on the lungs against acute injury induced by sepsis.