δ阿片受体激动剂DADLE对脓毒症大鼠神经内分泌免疫网络的影响

Effect of DADLE on the changes of neuroendocrine-immune system in rats with sepsis

目的研究δ阿片受体激动剂DADLE对脓毒症大鼠神经内分泌-免疫网络的调节作用。方法选用72只SD大鼠随机分为假手术组(SO)、脓毒症组(SEP)、DADLE组[制模后腹腔内注射DADLE(5mg/kg)],每组24只。盲肠结扎穿孔(CLP)建立脓毒症模型,制模后于6小时,12小时,24小时各取8只处死取材,ELISA法检测血清ACTH、CORT浓度。CLP后24小时处死的8只大鼠,取脑组织进行α7nAChR定量检测。结果脓毒症组(SEP)及DADLE组6小时,12小时,24小时后血清ACTH水平均显著高于假手术组(SO)(P<0.05),DADLE组血清ACTH及CORT水平各时间点均低于脓毒症组(SEP)(P<0.05)。SEP组12小时、24小时血清ACTH及CORT均显著高于6小时(P<0.05),SEP组24小时血清ACTH浓度高于12小时,但CORT浓度较12小时降低(P<0.05)。DADLE组24小时血清ACTH、CORT浓度显著低于12小时,但仍高于6小时(P<0.05)。DADLE处理组α7nAChR量明显高于假手术组和脓毒症组(P<0.05)。结论DADLE激活胆碱能抗炎通路,增加α7nAChR的表达,减少炎症因子释放;并通过降低血清ACTH、CORT水平来干预下丘脑-垂体-肾上腺(HPA)轴,减轻脓毒症大鼠的过度应激状态。

Objective To observe the effect ofδopioid receptor agonist(DADLE)on neuroendocrine-immune system in septic rats.Methods seventy-two SD rats were randomly divided into sham operation group(SO),sepsis group(SEP),DADLE group[intraperitoneal injection of DADLE(5mg/kg)],24 rats in each group.Model of sepsis was established by cecal ligation and perforation(CLP).The serum ACTH,CORT concentration was detected by ELISA.The quantity ofα7nAChR in ratbrain tissue was detected by PCR.Results The serum ACTH levels inSEPgroup and DADLE group were significantly higher than those in SO group(P<0.05),DADLE and SEP(P<0.05).In SEP group at each time point,the serum ACTH and CORT in 24h were significantly higher than those in 6h(P<0.05).The serum ACTH concentration in 24h was higher than that in 6h.At 12h,the concentration of CORT was lower than that of 12h(P<0.05).The concentration of serum ACTH,CORT at24h was significantly lower than that at12h,but still higher than that at6h(P<0.05).Compared with the SEP group,theα7nAChR in brain tissue significantly increased in DADLE group.Conclusion DADLE`s influence on NEI include increasing the level ofα7nAChR and decrease the inflammatory factor of sepsis rats,and reducing the level of serum ACTH,CORT to interfere with the hypothalamus-pituitary-adrenal(HPA)axis that relieve the excessive stress state of sepsis rats.