δ阿片受体激动剂对脓毒症大鼠肺功能的保护作用

Protective Effect of DADLE on Pulmonary Function in Rats with Sepsis

目的探讨δ阿片受体激动剂DADLE(D-Ala2-D-Leu5-enkephali)对脓毒症大鼠肺功能保护作用及其机制。方法SD大鼠72只,分为假手术组(SO组)、脓毒症组(SEP组)和DADLE给药组(DADLE组),每组24只。采用改良盲肠结扎穿孔方法(CLP)建立大鼠脓毒症模型,SO组除不结扎、刺穿盲肠外,其余操作同SEP组,DADLE组模型建立后立即按5 ml/kg体重静脉注射浓度为0.5 mg/ml的DALDE。于手术后2、6、10 h开腹取血行动脉血气分析;测定肺组织湿/干重(W/D)比值;测定肺组织匀浆中髓过氧化物酶(MPO)、丙二醛(MDA)、三磷酸腺苷(ATP)含量;检测血浆中肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)含量;观察并比较各组肺组织病理改变。结果与SEP组相比,DA-DLE组PaCO2、PaO2均明显提高(P<0.05);W/D值明显降低(P<0.05);肺组织MPO、MDA含量明显降低(P<0.05),ATP含量明显升高(P<0.05);血浆TNF-α和IL-6含量明显降低(P<0.05);肺组织病理学改变明显减轻。结论δ阿片受体激动剂DADLE对脓毒症大鼠肺功能具有一定的保护作用。

Objective To study the protective effects of DADLE on pulmonary function in rats with sepsis and the mechanism.Methods Seventy-two SD rats were randomly divided into sham operated group（SO）,septic group（SEP）,and DADLE-treated group（DADLE）.Sepsis model was induced by cecal ligation and puncture（CLP）.In SO group,the abdomen was opened without any other treatment.In DADLE-treated group,DADLE（0.5 mg/ml）was administerd at a dose of 5 ml/kg by intravenous injection after CLP.Rats were sacrificed at the 2nd,6th and 10th h after CLP.Arterial blood was collected for blood gas analysis.The wet-to-dry lung weight ratio was measured,and the levels of TNF-α and IL-6 in blood were detected.The levels of MPO,MDA and ATP in lung tissue were determined.The pathologic changes of the lungs were examined under a light microscope.Results As compared with SEP group,PaCO2,and PaO2 were significantly increased（P〈0.05）,while the wet-to-dry ratio and levels of serum TNF-α and IL-6 were significantly reduced（多P〈0.05）,and levels of MPO and MDA were significantly reduced（P〈0.05）and content of ATP in lung tissue was significantly increased（P〈0.05）in DADLE group.More severe pathological changes were found in SEP group than in DADLE group.Conclusion DADLE has pulmonary protective effects in rats with sepsis.