δ阿片受体激动剂DADLE对脓毒症大鼠急性肺损伤的保护作用

摘要

Objective To investigate the potective effect of δ-opiold receptor agonist DADLE on acute lung injury (ALI) in rat model induced by sepsis.Methods Totally 96 Sprague-Dawley (SD) rats were randomly divided into four groups including sham-operated group (SHAM group),ALI group (ALI group),Glucocorticoid treated group (GC group) and DADLE treated group (DADLE group),and each group had 24 rats.ALI model was produced by cecal ligation and puncture (CLP).In SHAM group,the abdomen was opened and then closed without any other treatment.In DADLE group,DADLE was administered at a dose of 5 ml/kg by intravenous injection after CLP.ALI models were treated with GC at a dose of 2.5 ml/kg in GC group.All of them were sacrificed at reparately 3,6 and 12h after CLP.Then arterial blood gas were analyzed.Meanwhile the renous blood was collected for assaying tumor necrosis factor-α (TNF-α),intedeukin-6 (IL-6) and nuclear factor-kappaB (NF-κB).Results As compared with the ALI group,PaCO2,PaO2,HCO3-and BE of GC and DADLE groups were significantly increased (P ＜ 0.05),while the levels of serum TNF-α,IL-6 and NF -κB were apparently reduced in GC and DADLE groups,but there was no difference between the DADLE group and the GC group (P ＞0.05).Different pathological degrees of cellular damage,inflammatory cell infiltration and interstitial edema were found in lungs,and all these damages in DADLE group and GC group were slighter than those in ALI group.Conclusion Dealing with DADLE on rats with sepsis can improve the lung function and reduce the level of cytokines.Compared with the GC,DADLE has the similarly anti-inflammatory function.%目的 探讨δ阿片受体激动剂DADLE对脓毒症性急性肺损伤(ALI)的保护作用.方法 采用盲肠结扎穿孔法(CLP)制作脓毒症急性肺损伤模型,将模型随机分为ALI组、假手术组(SHAM组)、糖皮质激素(GC)治疗组和DADLE治疗组.分别于建模3、6和12h后开腹抽血行动脉血气分析,ELISA法检测血浆中肿瘤坏死因子-α(TNF-α)、白介素-6(IL-6)和核因子-κB(NF-κB)的含量,观察与比较各组肺组织病理改变.结果 DADLE组中PaCO2、PaO2、HCO2-和BE与GC组相比较差异无统计学意义(P＞0.05),但均高于ALI组(P＜0.05)；GC组和DADLE组血浆中TNF-α、IL-6和NF-κB水平均明显低于ALI组(P＜0.01)；DADLE组和GC组肺组织病理学变化均较ALI组轻.结论 DADLE对脓毒症大鼠的肺组织有明确的保护作用,具有抑制炎性细胞因子释放作用,其抗炎作用与GC相似.