辛伐他汀对糖基化终末产物致大鼠血管内皮功能损伤的保护作用  

Protective Effects of Simvastatin on Impaired Vascular Endothelial Function Induced by AGEs

作　　者：李先霞[1] 刘克清[1] 凌伯勋[1] 方叶青[2] 

机构地区：[1]岳阳职业技术学院,湖南岳阳414000 [2]中南大学湘雅医院,湖南长沙410008

出　　处：《岳阳职业技术学院学报》2008年第4期71-76,共6页Journal of Yueyang Vocational and Technical College

基　　金：湖南省科技计划项目"辛伐他汀对糖基化终末产物致血管内皮功能损伤的保护作用"(2007GK3065)

摘　　要：目的:探讨辛伐他汀对外源性制备的糖基化终末产物损伤大鼠离体胸主动脉环内皮依赖性舒张功能的影响及其机制。方法:按文献方法制备糖基化终末产物,采用外源性糖基化终末产物(AGE-BSA)孵育大鼠离体胸主动脉环90min诱导血管内皮功能的损伤,并观察辛伐他汀、超氧化物歧化酶和L-精氨酸对糖基化终末产物致的血管内皮依赖性舒张功能损害的影响。结果:外源性糖基化终末产物孵育大鼠离体胸主动脉环90min,明显抑制乙酰胆碱诱导的内皮依赖性血管舒张反应(endothelium-dependent relaxation,EDR)。但对硝普钠诱导的内皮非依赖性血管舒张反应没有影响。辛伐他汀(0.05,0.1,0.2μmol/L)与AGE-BSA共同孵育血管环90min,浓度依耐性地改善AGE-BSA对血管内皮依赖性舒张功能的损害。氧自由基清除剂超氧化物歧化酶(superoxide dismutase,SOD,200U/mL)也可逆转AGE-BSA对内皮依赖性血管舒张反应的损害,而L-精氨酸(L-arginine,L-Arg,3mmol/L)却只有部分保护作用。而且,辛伐他汀也能取消SOD抑制剂二乙基二硫氨甲酸酯(diethyldithiocarbamate,DETC;10μmol/L)诱导产生内源性氧自由基所致的血管内皮依赖性反应的抑制。结论:辛伐他汀能取消AGE-BSA对大鼠离体胸主动脉环血管内皮依赖性舒张反应的抑制,该保护作用可能与其抗氧化作用有关。Purpose： To explore whether simvastatin exerts beneficial effect on impaired vascular endothelial function elicited by exogenous AGEs and to investigate the potential mechanisms. Method： Exogenous glycosylated bovine serum Albumin （AGE-BSA） was prepared according to the methods of article. The rings were respectively incubated with exogenous AGEs to induce endothelial dysfunction. In the drug-treated groups, aortic rings were incubated with drug for 15 min and then exposed to AGE-BSA for another 90 min in the presence of the drug, such as simvastatin, SOD and L-arginine. Vasodilator responses to acetylcholine （ACh） or sodium nitroprusside （SNP） of aortic rings were measured by isometric tension recording after drag treatment. Results： Results from in vitro experiments showed that a 90min incubation of aortic tings with AGEs resulted in a significant inhibition of EDR, but had no effects on endothelium-independent relaxation. Pre-incubation of aortic rings with simvastatin（0.05,0.1 ,0.2μmol/L）for 15 min and co-incubation of aortic rings with AGE-BSA for another 90 rain significantly alleviated the inhibition of endothelium-dependent relaxation induced by AGE-BSA in a dose-dependent manner. SOD （200U/mL）, a scavenger of superoxide anions, can also markedly attenuated the inhibition of EDR caused by AGE-BSA, but L-Arg had only partly protective effects on impaired EDR induced by AGE-BSA. Moreover, simvastatin （0.2μmol/L） also alleviated impairment of endothelium-dependent relaxation of rat aortic ring induced by endogenous oxygen free radicals generated by diethyldithiocarbamate （DETC ,10 μmol/L） via inhibiting intracellular SOD. Conclusion： Simvastatin can protect against vascular endothelial dysfunction caused by AGE-BSA. The protective effects of simvastatin may be involved in its anti-oxidation.

关 键 词：辛伐他汀 糖基化终末产物 超氧化物歧化酶 内皮依赖性舒张 

分 类 号：R972[医药卫生—药品]