δ阿片受体激动剂对脓毒症大鼠肾脏保护作用的研究

Study of δ-opioid receptor agonist on renal protection in rat with sepsis

目的探讨δ阿片受体激动剂DADLE对脓毒症大鼠肾脏保护作用及其机制。方法选择SD大鼠72只,平均分为假手术组(SHAM组)、脓毒症组(SEP组)和DADLE组,改良盲肠结扎穿孔方法(CLP)建立大鼠脓毒症模型,SHAM组打开腹腔后关膜,DADLE组模型建立后立即按5 mL/kg剂量静脉注射DALDE。在制模后2 h、6 h和10h杀死每组8只大鼠,检测血肌酐(Cr)、血尿素氮(BUN)、肿瘤坏死因子α(TNF-α)和白细胞介素-6(IL-6),取左肾组织测ATP含量。结果血BUN:与SHAM组比较,SEP组和DADLE组在3个时间点均有显著升高(P均<0.05);与SEP组比较,DADLE组血BUN在6 h1、0 h均有明显降低(P均<0.05)。血Cr:与SHAM组比较,SEP组和DA-DLE组在10 h有显著升高,但DADLE组低于SEP组。血TNF-α、IL-6:与SHAM组比较,SEP组和DADLE组在各时间点均明显升高,而DADLE组明显低于SEP组。肾ATP:与SHAM组比较,SEP组和DADLE组在各时间点均明显下降,而DADLE组明显高于SEP组。结论DADLE处理脓毒症大鼠,可以显著减少肾组织ATP的下降,降低细胞因子的水平,改善肾功能。

Objective It is to study the renal protective effect and its mechanism of δ- opioid receptor agonist （DADLE） on rats with sepsis. Methods 72 SD rats were randomly divided into sham operated group（SHAM）, septic group（SEP）, DADLE group. 8 Rats in each group were sacrificed at 2 h, 6 h and 10 h after making model. Sepsis model was established by cecal ligation and puncture （CLP）. In SHAM group,the abdomen of the rats was opened without any other treatment. In DADLE group,DADLE was administer at a dose of 5 mL/kg by intravenous injection after CLP. The serum levels of Cr, BUN, TNF-α and IL-6 were detected at every time point,ATP contents were measured from left kidney tissue. Results Compared with the SHAM group,the serum levels of BUN in both SEP and DADLE groups were significantly higher at all times （P 〈 0.05）, and the levels in the DADLE group were significantly lower than that in SEP group at 6h and 10 h（P 〈 0.05）. Compared with the SHAM group,the serum levels of Cr in both SEP and DADLE groups were higher at 10 h, but the DADLE group data were lower than SEP group at 10 h, and the differences were significant among the three groups （P 〈 0.05）. Compared with the SHAM group, the levels of serum TNF- α and I L 6 in both DADLE and SEP groups rose, and the DADLE group data were obviously lower than the SEP group. The differences were significant among the three groups. Compared with the SHAM group, the levels of ATP in the renal tissue in both DADLE and SEP groups decreased significantly, and the DADLE group data were higher than the SEP group. The differences were significant among the three groups. Conclusion Dealing with DADLE on septic rats can reduce the decline of ATP contents in renal tissue and the level of cytokines, and can improve the renal function