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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 investigate the protective effect of δ-opioid receptor agonist DADLE (D-Ala2-D-Leu5-enkephali) on pulmonary function in septic rats and its mechanism. Methods Seventy-two SD rats were divided into sham operation group (SO group), sepsis group (SEP group) and DADLE administration group (DADLE group), 24 rats in each group. The sepsis model of rats was established by modified cecal ligation and puncture (CLP). In addition to the ligation and puncture of cecum in SO group, the other operations were the same as those of SEP group. The model of DADLE group was established immediately after injection of 5 ml / kg body weight intravenously 0.5 mg / ml DALDE. The blood samples were collected at 2, 6 and 10 h after surgery for arterial blood gas analysis. The wet / dry weight (W / D) ratio of lung tissue was measured. The levels of myeloperoxidase (MPO), malondialdehyde MDA, and ATP were detected. The levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in plasma were measured and the pathological changes of lung tissues were observed and compared. Results Compared with SEP group, PaCO2 and PaO2 in DA-DLE group increased significantly (P <0.05), W / D value decreased significantly (P <0.05), MPO and MDA content in lung tissue decreased significantly (P <0.05). The contents of TNF-α and IL-6 in plasma were significantly decreased (P <0.05). The pathological changes in lung tissue were significantly reduced. Conclusion D opioid receptor agonist DADLE has a protective effect on pulmonary function in septic rats.