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

摘要

OBJECTIVE:To study the protective effects of soluble ornithine cyclase activator cinaciguat(called CIN 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(P0.05). Compared with normal group,MDA content and mRNA expression of ICAM-1 and VCAM-1 increased in high glucose group,while SOD activity decreased(P0.05). Compared with high glucose group,MDA content and mRNA expression of ICAM-1 and VCAM-1 decreased in high glucose+CIN 1 µmol/L group,while SOD activity increased(P<0.05). CONCLUSIONS:CIN can protect high glucose-induced HUVECs injury in vitro. The mechanism may be associated with in-hibition of oxidative stress and inflammatory response.%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）mRNA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 mRNA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 mRNA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。