洛伐他汀对HTL损伤血管内皮功能的保护作用及机制探讨  

Protective effect and mechanism of lovastatin on vascular endothelial dysfunction induced by homocysteine thiolactone

作　　者：黄宁江[1] 吴树金[2] 杨旭红[2] 刘立英[2] 

机构地区：[1]永州职业技术学院药理学教研室,湖南永州425000 [2]中南大学药学院,长沙410078

出　　处：《中南药学》2009年第1期17-20,共4页Central South Pharmacy

摘　　要：目的探讨洛伐他汀对同型半胱氨酸硫内酯(Homocysteine Thiolactone,HTL)所致在体大鼠血管内皮功能损伤的保护作用及其机制。方法采用HTL 50 mg.kg-1灌胃8周的方法制造在体大鼠血管内皮损伤模型,同时治疗组给予洛伐他汀10、40 mg.kg-1灌胃。8周后检测血管内皮依赖性舒张反应、血清中一氧化氮、丙二醛的含量及总胆固醇、甘油三酯的水平,超氧化物歧化酶、谷胱甘肽过氧化物酶的活性,血管组织中NF-κBP65的表达。结果洛伐他汀呈剂量依赖性地改善HTL抑制的大鼠胸主动脉的内皮依赖性舒张反应,增强血清中超氧化物歧化酶、谷胱甘肽过氧化物酶的活性,升高一氧化氮水平、降低丙二醛的含量,同时抑制血管组织中NF-κBP65表达的增加,与HTL损伤组相比差异均有显著性(P<0.05或P<0.01)。各组大鼠血脂水平无明显变化。结论洛伐他汀对HTL所致在体大鼠血管内皮功能损伤具有显著保护作用,其作用机制可能与洛伐他汀的抗氧化作用有关,而不依赖于其降脂的作用。Objective To explore the protective effect and the potential mechanism of lovastatin on endothelial dysfunction induced by homocysteine thiolactone （HTL）. Methods The rat model of vascular endothelium injured by intragastric gavaged homocysteine thiolactone （ HTL, 50 mg · kg^-1 ） was established, and the intervention groups were given intragastric gavaged lovastatin （10, 40 mg · kg^-1 ）. After 8 weeks of treatment, endothelium-dependent relaxation （EDR） of aortic rings were examined. Contents of nitro oxide （NO）, malondialdehyde （MI）A）, total cholesterol （TC） and triglyeride （TG）, the acitivity of superoxide dismutase （SOD） in the sera and the expression of nuclear factor-kBP65 （NF-kBP65） in vascular endothelium were analyzed. Results Compared with the HTL group, lovastatin markedly improved the EDR, maintained the level of NO, decreased the level of MDA, improved the activation of SOD in the sera, and simultaneously inhibited the expression of NF-kBP65 in vascular endothelium （P〈0. 05 or P〈0. 01）. There was no significant difference in the lipoprotein serum level among all groups. Conclusion Lovastatin could significantly protect from impairment of vascular endothelium function in rats induced by HTL. The mechanism may relate to the anti-oxidation effect of lovastatin, instead of its cholesterol-lowering manner.

关 键 词：洛伐他汀 HTL 内皮依赖性舒张反应 氧化应激 

分 类 号：R961[医药卫生—药理学]