可溶性鸟苷酸环化酶激活剂Cinaciguat对高糖环境下人脐静脉内皮细胞的保护作用  

Protective Effects of Soluble Ornithine Cyclase Activator Cinaciguat on Human Umbilical Vein Endothelial Cells under the Condition of High Glucose

作　　者：李亚楠[1] 孙冰[2] 班博[2] 张国安[3] 赵奇[1] 张梅[2] 

机构地区：[1]山东大学医学院,济南250100 [2]济宁医学院附属医院内分泌科,山东济宁272000 [3]济宁医学院病理生理学实验室,山东济宁272000

出　　处：《中国药房》2016年第7期886-888,共3页China Pharmacy

基　　金：山东省自然科学基金资助项目(No.ZR2012HL25);山东省高校优秀科研创新团队

摘　　要：目的:研究可溶性鸟苷酸环化酶激活剂Cinaciguat(以下简称CIN)对高糖环境下人脐静脉内皮细胞(HUVECs)的保护作用。方法:以33.3 mmol/L的葡萄糖作用于HUVECs细胞复制氧化应激损伤模型。将HUVECs细胞分为正常组、高糖组和高糖+CIN 0.01、0.1、1、10μmol/L组,采用MTT法检测细胞活力,计算细胞存活率;另将HUVECs细胞分为正常组、正常+CIN 1μmol/L组、高糖组、高糖+CIN 1μmol/L组,采用硫代巴比妥酯法、黄嘌呤氧化酶法检测细胞中丙二醛(MDA)含量和超氧化物歧化酶(SOD)活性,采用实时荧光定量聚合酶链反应法检测细胞中细胞间黏附分子1(ICAM-1)、血管细胞黏附分子1(VCAM-1)m RNA的表达。结果:与正常组比较,高糖组细胞存活率降低(P<0.05);与高糖组比较,高糖+CIN 0.01、0.1、1、10μmol/L组细胞存活率升高(P<0.05),且呈浓度依赖性,但高糖+CIN 1μmol/L组与高糖+CIN 10μmol/L组间细胞存活率差异无统计学意义(P>0.05)。与正常组比较,高糖组细胞中MDA含量增加、SOD活性降低、ICAM-1和VCAM-1 m RNA表达增强(P<0.05),但正常+CIN 1μmol/L组细胞上述指标无明显变化(P>0.05);与高糖组比较,高糖组+CIN 1μmol/L组细胞中MDA含量降低、SOD活性增强、ICAM-1和VCAM-1 m RNA表达减弱(P<0.05)。结论:CIN对体外高糖诱导的HUVECs细胞损伤具有保护作用,其机制可能与抑制氧化应激和炎症反应有关。OBJECTIVE： To study the protective effects of soluble omithine cyclase activator cinaciguat （called C1N for short） on human umbilical vein endothelial cells （HUVECs） under the condition of high glucose. METHODS： HUVECs were treated with glucose 33.3 mmol/L to induce oxidative stress injury model. HUVECs were divided into normal group, high glucose group and high glucose＋CIN 0.01, 0.1, 1 and 10 μmol/L groups. The cell viability was detected by MTT assay, and the survival rate of cells was callulated. Besides, HUVECs were divided into normal group, normal＋CIN 1 μmol/L group, high glucose group, high glucose＋CIN 1 μmol/L group. MDA content and SOD activity were determined by TBA method and xanthine oxidase method; mRNA expression of ICAM-1 and VCAM-1 were determined by RT-PCR. RESULTS： Compared with normal group, survival rate decreased in high glucose group （P〈0.05）; compared with high glucose group, that increased in high glucose＋CIN 0.01, 0.1, 1 and 10 μmol/L groups, in concentration-dependent manner; there was no statistical significance in survival rate between high glucose＋CIN 1 μmol/L group and high glucose＋CIN 10 μmol/L group （P〉0.05）. Compared with normal group, MDA content and mRNA expression of ICAM-1 and VCAM-1 increased in high glucose group, while SOD activity decreased （P〈0.05） ; above indicators had no significant change in normal＋C1N 1 μmol/L group （P：〉0.05）. Compared with high glucose group, MDA content and mRNA expression of ICAM-1 and VCAM-1 decreased in high glucose＋ClN 1μmol/L group, while SOD activity increased （P〈 0.05 ） . CONCLUSIONS： C1N can protect high glucose-induced HUVECs injury in vitro. The mechanism may be associated with inhibition of oxidative stress and inflammatory response.

关 键 词：Cinaciguat 高糖 人脐静脉内皮细胞 氧化应激 炎症反应 

分 类 号：R965[医药卫生—药理学]