摘要
目的探讨κ阿片受体在血管紧张素Ⅱ诱导内皮细胞产生白介素-6和白介素-8中的作用。方法整体实验观察大鼠静脉注射U50488H（1.5 mg.kg^-1）后血中AngⅡ水平的变化;体外培养人脐静脉内皮细胞,分为对照组、AngⅡ组、AngⅡ＋U50488H组,AngⅡ＋U50488H＋nor-BNI（κ阿片受体阻断剂）组。分别用磷酸盐缓冲溶液、AngⅡ（10^-9-10^-5mol.L^-1）或提前给予κ阿片受体激动剂或（和）阻断剂诱导0-24 h,收集0、3、6、12、24 h等时间点的细胞培养液,采用酶联免疫吸附法分别检测细胞培养液IL-6和IL-8水平。结果静脉注射U50488H可明显降低血中AngⅡ的水平,该作用可被nor-BNI（2 mg.kg^-1）所阻断。AngⅡ可浓度和时间依赖性诱导内皮细胞产生释放IL-6和IL-8,提前给予U50488H（10-5mol.L^-1）可明显抑制AngⅡ诱导内皮细胞产生释放IL-6和IL-8。而nor-BNI（10^-5mol.L^-1）本身没有任何作用但可完全阻断U50488H的上述作用。结论 U50488H可通过下调AngⅡ水平和抑制AngⅡ的作用来减少内皮细胞产生IL-6和IL-8,表明κ阿片受体可能在抗炎中具有一定调节作用。
Aim To examine the effect of κ opioid receptor agonist U50488H on the levels of interleukin-6（IL-6） and interleukin-8（IL-8） from angiotensinⅡ（AngⅡ） stimulated endothelial cells.Methods In the in vivo study,the modulation of U50488H（1.5 mg·kg-1） intravenously on the level of AngⅡ was evaluated.In the in vitro study,endothelial cells from human umbilical vein（HUVEC） were cultured and divided into four groups：Control group,AngⅡ group,and AngⅡ plus U50488H and/or nor-BNI（a selective κ opioid receptor antagonist） group.These groups were treated respectively with phosphate buffered solution（PBS）,AngⅡ（10-9-10-5 mol·L-1）,and AngⅡ in the presence of U50488H and/or nor-BNI for 0-24 hours.Culture supernatant and endothelial cells were collected at 0,3,6,12 and 24 h.IL-6 and IL8 levels in culture supernatant were measured by enzyme linked immunosorbent assay（ELISA）.Results The level of AngⅡ in the blood was significantly decreased following U50488H intravenously,which was blocked by nor-BNI administration（2 mg·kg-1）.AngⅡ stimulated the productions of IL-6 and IL-8 from HUVEC in the dose-dependent and time-dependent manners.U50488H at 10-5 mol·L-1 significantly inhibited this process,and the inhibitory effect of U50488H was blocked by nor-BNI,which itself had no effect.Conclusion κ opioid receptor may play a role in the process of anti-inflammation via down regulation of AngⅡ level and inhibition of the AngⅡ-stimulated IL-6 and IL-8 productions from endothelium cells.
出处
《中国药理学通报》
CAS
CSCD
北大核心
2010年第7期922-925,共4页
Chinese Pharmacological Bulletin
基金
国家自然科学基金资助项目(No30770802
30971060)
