二甲双胍对低密度脂蛋白诱导的大鼠血管内皮功能紊乱的改善作用

Protective effects of metformin on low-density lipoprotein-induced endothelial dysfunction in rats

目的研究二甲双胍是否对低密度脂蛋白损伤的大鼠血管内皮功能具有保护作用并探讨其机制。方法一次性从大鼠舌下静脉注射天然低密度脂蛋白(n-LDL)4mg/kg诱发血管内皮细胞损伤,随后测定血管舒张功能及血脂,血清一氧化氮(NO)、丙二醛(MDA)和SOD活性。结果单次静脉注射n-LDL能降低大鼠胸主动脉乙酰胆碱诱导的内皮依赖性舒张反应,而对硝普钠诱导的非内皮依赖性舒张反应无影响;血清NO水平及SOD活性显著降低,MDA浓度明显增高而血脂水平无明显变化。二甲双胍预处理能改善n-LDL诱导的内皮舒张功能障碍,增加血清NO水平,减少MDA生成,不改变血脂含量。结论二甲双胍对体内LDL损伤的血管内皮功能具有保护作用,其机制可能与二甲双胍保护内皮依赖性舒张因子和抗氧化作用有关。

Objective To observe the protective effect ofmetformin on the endothelial function and the mechanisms in rats with low-density lipoprotein （LDL） injection. Methods A single dose （4 mg/kg） of natural LDL was injected through the sublingual vein of rats to induce vascular endothelial dysfunction. Blood samples were then collected from the rats to detect the concentrations of malondialdehyde （MDA） and nitric oxide （NO）, activity of superoxide dismutase （SOD） and serum lipid levels. The thoracic aorta of rats was obtained to assay acetylcholine （ACh）-induced endothelium-dependent relaxation （EDR） and sodium nitroprusside （SNP）-inducedendothelium-independentrelaxation. The effects of metformin pretreatment on the endothelial functions in the rats were investigated. Results A single-dose LDL significantly inhibited ACh-indueed EDR without affecting SNP-induced endothelial-independent relaxation. The injection decreased serum NO and elevated serum MDA level, but had no effect on serum lipid level. Metformin markedly attenuated LDL-induced inhibition of EDR, serum MDA elevation, and serum NO reduction without affecting the serum lipid levels. Conclusion Metformin provides protection against vascular endothelial dysfunction induced by LDL in rats, the mechanism of which is probably associated with protection of endothelium-dependent relaxation factor and inhibition of the oxidative stress.