别嘌呤醇对高糖诱导损伤的人脐静脉血管内皮细胞的保护作用

The protective effect of allopurinol on injury of HUVEC induced by high glucose

目的探讨别嘌呤醇对高糖损伤后的人脐静脉血管内皮细胞（HUVEC）的保护作用及其机制。方法以HUVEC为研究对象，体外培养至第三代，分为：①20mmol／L高糖损伤对照组；②别嘌呤醇保护组（浓度分别为0．1mmol／L、0．2mmol／L、0．3mmol／L）；③维生素C阳性对照组（浓度为100mg／L）。不同浓度别嘌呤醇及维生素C先与HUVEC孵育24h，再加入20mmol／L高糖诱导损伤48h，测定各组细胞上清液中一氧化氮（NO）、丙二醛（MDA）、超氧化物歧化酶（SOD）、细胞间黏附分子-1（ICAM-1）含量及细胞凋亡率。结果别嘌呤醇（0．1mmol／L、0．2mmol／L、0．3mmol／L）药物保护组的细胞凋亡率低于20mmol／L高糖组，其中以0．3mmol／L更为明显（P〈0．01）；细胞培养液中SOD、NO的量均较20mmol／L高糖组增高，其中以0．3mmd／L别嘌呤醇组更为明显（P〈0．01）。药物保护组细胞培养液中合成MDA、ICAM-1较波动性高糖组降低，且在一定浓度范围内（0．05-49．30mmol／L）呈浓度依赖性（P〈0．05）。结论①别嘌呤醇对高糖体外诱导的HUVEC损伤有保护作用，呈浓度依赖性。②别嘌呤醇对高糖体外诱导HUVEC损伤保护作用的机制包括抑制氧化应激、炎症反应及细胞凋亡。

Objective To observe the protective effect of allopurinol on high glucose -induced injured vascular endothelial cell （VEC）, and discuss its mechanism. Methods Cultured human umbilical vein endothelial cells in vitro to third-generation. The experiment was divided into three groups： （1）20 mmol/L glucose injured group. （2）Allopurinol protective group （Concentrations were 0.1 mmol/L, 0.2 mmol/L and 0.3 mmol/L respectively）. （3）Vitamine C positive control group （Concentration was 100 mg/L）. Allopurinol and vitamine C with different concentrations were incubated with HUVEC for 24 hours firstly. Then, 20 mmol/L high glucose was added inter- mittently to induce injury. The content of MDA, SOD, NO, ICAM-1 and apoptosis rate in cell supernatant for each group was measured. Results The apoptosis rate in allopurinol drug-protective group （0.1 mmol/L, 0.2 mmol/L and 0.3 mmol/L） was lower than 20 mmol/L high glucose group, in which 0.3 mmol/L was more significant （P〈0.01）. The contents of SOD and NO in culture of this group were increased more than 20 mmol/L high glucose group, in which 0.3 mmol/L allopurinol group was more significant （P〈0.01）. The content of MDA and ICAM-1 in culture of drug-protective group was lower than high glucose group, which showed a concentration dependent manner in a certain concentration range （0.05-0.30 retool/L） （P〈0.05）. Conclusion （1）Allopurinol has a protective effect on the injury of HUVEC induced by high glucose that shows a concentration dependent manner. （2）The mechanism of protective effect of allopurinol on the injury of HUVEC induced by high glucose includes inhibition of oxidative stress, inflammation and apoptosis.