目的:探讨洛伐他汀与格列本脲联合用药对高糖诱导损伤的人脐静脉血管内皮细胞(HUVEC)的功能的影响及其机制。方法:以体外培养至第三代的HUVEC为研究对象,分四为:1空白对照组;2高糖组(33 mmol/L);3高糖组(33 mmol/L)+洛伐他汀(2μmol/L)组;4高糖组(33 mmol/L)+洛伐他汀(2μmol/L)+格列本脲(0.2μmol/L)组。用transwell小室法检测HUVEC的迁移功能,用细胞流式仪检测HUVEC内氧自由基(O^2-)以及一氧化氮(NO)的表达水平。结果:与对照组相比,高糖组HUVEC迁移功能明显受损(P〈0.01);洛伐他汀单独用药组及其与格列本脲的联合用药组均能改善高糖损伤的HUVEC的迁移功能(均为P〈0.01)。流式结果显示,与对照组相比,高糖组HUVEC内O^2-水平明显增加而NO表达水平明显降低(均为P〈0.01);两组给药组HUVEC内O^2-水平及NO表达水平相对于高糖组均有明显改善(均为P〈0.01)。结论:洛伐他汀单独用药及其与格列本脲的联合用药均能改善高糖损伤的HUVEC的迁移功能,可能与改善细胞内氧化应激水平有关。
Objective: To investigate the effect of lovastatin and glyburide combination therapy on high glucose-induced damage of human umbilical vein endothelial cells(HUVEC) function and its possible mechanism. Methods: The third generation of HUVEC cultured in vitro were selected for the study, and divided into four groups as follows: 1control group; 2high glucose(33 mmol/L)group; 3high glucose(33 mmol/L) + lovastatin(2 μmol/L) group; 4high glucose(33 mmol/L) + lovastatin(2 μmol/L) + glyburide(0.2μmol/L) group. The migration of HUVEC was observed with transwell chambers, and the level of oxygen free radicals(O^2-) and nitric oxide(NO) expression was detected by flow cytometer. Results: Compared with the control group, the migration of HUVEC was obviously damaged in the high glucose group(P〈0.01); compared with the high glucose group, the migration of HUVEC was obviously improved in the groups of lovastain monotherapy and combination therapy with glibenclamide(P〈0.01). Flow cytometry results showed that the level of O^2- expression in the HUVEC was increased and NO expression in the HUVEC was decreased in the high glucose group compared with the control group(P〈0.01); and the level of O^2-and NO expression in the HUVEC was obviously improved in the groups of lovastain monotherapy and combination therapy with glibenclamide(P〈0.01). Conclusions: Lovastatin monotherapy and combination therapy with glibenclamide's can improve the migration of HUVEC, which may be associated with improved intracellular oxidative stress and NO levels.