δ阿片受体激动剂对脓毒症大鼠细胞免疫功能的影响

Effect of δ-opioid receptor agonist on celinar immune function in a rat model of sepsis

目的探讨δ阿片受体激动剂对脓毒症大鼠细胞免疫功能的影响。方法健康成年雄性SD大鼠150只，体重154～198g，随机分为3组（n=50）：假手术组（S组）仅穿线，不进行盲肠结扎穿孔；脓毒症组（SEP组）采用盲肠结扎穿孔的方法制备脓毒症模型；δ阿片受体激动剂组（DADLE组）于盲肠结扎穿孔后立即腹腔注射δ阿片受体激动剂DALDE10ml／kg，浓度为0．5mg／ml。于盲肠结扎穿孔后4、8、12h（L1-3）时各组随机取10只大鼠，抽取下腔静脉血样，采用ELISA法检测血清TNF—a和IL-10的浓度，采用流式细胞仪检测T淋巴细胞亚群变化。记录盲肠结扎穿孔后7d内大鼠的生存情况。结果与S组比较，SEP组和DADLE组各时点血清TNF—a和IL-10的浓度、TNF—a／IL-10比值升高，L时CD4＋T细胞水平和CD4＋／CD8＋降低，CD8＋T细胞水平升高（P〈0．05或0．01）；与SEP组比较，DADLE组T2，时血清TNF-a和IL-10的浓度、TNF-a／IL-10比值降低，L时CD4＋T细胞水平和CD4＋／CD8＋升高，CD8＋T细胞水平降低，盲肠结扎穿孔后7d内大鼠生存率升高（P〈0．05）。结论δ阿片受体激动剂可改善细胞免疫功能，从而减轻炎性反应，有利于脓毒症大鼠的预后。

Objective To investigate the effect of δ-opioid receptor agonist D-Ala2-D-Leu5-enkephalin （DADLE） on the celluar immune function in septic rats. Methods One hundred and fifty healthy male SD rats weighing 154-198 g were randomly divided into 3 groups （ n = 50 each） ： group I sham operation （group S） ; group II sepsis （group SEP） and group III DADLE. Sepsis was induced by cecum ligation and punture （CLP） in group II and III . In group III 0.5 mg/kg DADLE 10 ml/kg was injected intraperitoneally （IP） immediately after CLP operation. Seven day survival rate was calculated. Blood samples were collected from 10 animals at 4, 8 and 12 h after operation （T1-3） respectively in each group for determination of serum TNF-a and IL-10 concentrations by ELISA and changes in T-cell subsets by flow cytometry. Results CLP significantly increased serum TNF-a and IL-10 concentrations and TNF-a/IL-10 ratio at T1-3 and decreased CD4＋ and CD4＋/CD8＋ ratio and increased CD8 ＋ at T3 in group II as compared with group S （group I ）. DADLE treatment significantly attenuated the CLP- induced above changes. Seven-day survival rate was significantly higher in DADLE group than in CLP group. Conclusion δ-opioid receptor agonist DADLE can improve the celluar immune function of rats with sepsis and increase the survival rate.