κ-阿片受体激动剂对高尿酸血症大鼠血管内皮细胞功能的影响及机制研究  

Effect ofκ-Opioid Receptor Agonist on Vascular Endothelial Cell Function in Hyperuricemia Rats and Its Mechanism

作　　者：郑琴[1] 杨红 陈秋宏 李晓慧 金家贵[3] 吴奇 Zheng Qin;Yang Hong;Chen Qiuhong;Li Xiaohui;Jin Jiagui;Wu Qi(Department of Geriatrics,The First Affiliated Hospital of Chengdu Medical College,Chengdu 610500,China;Department of Cardiology,The Second Affiliated Hospital of Chengdu Medical College·Nuclear Industry 416 Hospital,Chengdu 610057,China;Department of Cardiology,The First Affiliated Hospital of Chengdu Medical College,Chengdu 610500,China)

机构地区：[1]成都医学院第一附属医院全科医学科,成都610500 [2]成都医学院第二附属医院·核工业四一六医院心血管内科,成都610057 [3]成都医学院第一附属医院心血管内科,成都610500

出　　处：《成都医学院学报》2022年第5期561-564,共4页Journal of Chengdu Medical College

基　　金：四川省教育厅基金重点项目(No:18ZA0150);四川省教育厅基金一般项目(No:18ZB0177);成都市科技局科研项目(No:2022-YF05-01459-SN)。

摘　　要：目的探讨外源性κ-阿片受体(κ-OR)激动剂U50488H对高尿酸血症(HUA)大鼠血管内皮细胞功能的影响及其机制。方法将30只SD大鼠随机分为Control组、HUA组、HUA+U50488H组,每组10只,通过氧嗪酸钾灌胃建立HUA动物模型;取Control组的血管内皮细胞培养,将其分为Control组、HUA组、HUA+U50488H组、HUA+U50488H+κ-OR阻断剂(Nor-BNI)组、HUA+U50488H+蛋白激酶B(AKT)抑制剂组和HUA+U50488H+一氧化氮合酶抑制剂(L-NAME)组。采用酶联免疫吸附测定(ELISA)检测3组动物血清和6组细胞上清液的一氧化氮(NO)、内皮素-1(ET-1)及肿瘤坏死因子-α(TNF-α)的浓度,蛋白质印迹技术检测HUA大鼠血清与U50488H或PBS共同孵育内皮细胞后eNOS和AKT蛋白表达水平。结果在体内及体外实验中均显示,与Control组相比,HUA组NO、ET-1水平明显降低(P<0.05),TNF-α水平明显升高(P<0.05);与HUA组相比,HUA+U50488H组NO、ET-1水平明显升高(P<0.05),TNF-α水平明显降低(P<0.05)。大鼠血管内皮细胞的蛋白质印迹技术结果显示,与Control组相比,HUA组中eNOS和AKT的表达明显降低(P<0.05);与HUA组相比,U50488H组中eNOS和AKT的表达明显上升(P<0.05)。结论κ-OR激动剂U50488H可调节eNOS/AKT信号通路,改善HUA大鼠血管内皮细胞功能。Objective To investigate the effect of exogenousκ-opioid receptor(κ-OR)agonist(U50488H)on vascular endothelial cell function in rats with hyperuricemia(HUA)and its mechanism.Methods A total of 30 Sprague-Dawley(SD)rats were randomly divided into control group(n=10),HUA group(n=10)and HUA+U50488H group(n=10).HUA animal model was established by gavage of potassium oxazinate.The vascular endothelial cells of control group were cultured and divided into control group,HUA group,HUA+U50488H group,HUA+U50488H+κ-OR blocker(Nor-BNI)group,HUA+U50488H+protein kinase B(AKT)inhibitor group and HUA+U50488H+nitric oxide synthase inhibitor(L-NAME)group.The concentrations of nitric oxide(NO),endothelin-1(ET-1)and tumor necrosis factor-α(TNF-α)in rats serum and cell culture supernatant of each group were detected by enzyme linked immunosorbent assay(ELISA)method.The expression levels of endothelial nitric oxide synthase(eNOS)and AKT in endothelial cells incubated with U50488H or PBS in serum of HUA rats were detected by Western blot.Results In both rats serum and cell culture supernatant,the levels of NO and ET-1 in HUA group were significantly lower than those in control group(P<0.05),while the level of TNF-αin HUA group was significantly higher than that in control group(P<0.05);the levels of NO and ET-1 in HUA+U50488H group were significantly higher than those in HUA group(P<0.05),while the level of TNF-αin HUA+U50488H group was significantly lower than that in HUA group(P<0.05).Western blot assay of rat vascular endothelial cells showed that the expression levels of eNOS and AKT in HUA group were significantly lower than those in control group(P<0.05),while the expression levels of eNOS and AKT in U50488H group were significantly higher than those in HUA group(P<0.05).Conclusionκ-OR agonist U50488H can improve vascular endothelial cell function in rats with HUA by regulating eNOS/AKT signal pathway.

关 键 词：阿片受体激动剂 eNoS/AKT信号通路 高尿酸血症 血管内皮细胞功能 

分 类 号：R589.7[医药卫生—内分泌] R587.2[医药卫生—内科学]