CAJ | 학술논문

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。
목적：탐토신벌타정대외원성제비적당기화종말산물손상대서리체흉주동맥배내피의뢰성서장공능적영향급기궤제。방법：안문헌방법제비당기화종말산물，채용외원성당기화종말산물（AGE-BSA）부육대서리체흉주동맥배90min유도혈관내피공능적손상，병관찰신벌타정、초양화물기화매화L-정안산대당기화종말산물치적혈관내피의뢰성서장공능손해적영향。결과：외원성당기화종말산물부육대서리체흉주동맥배90min，명현억제을선담감유도적내피의뢰성혈관서장반응（endothelium-dependent relaxation，EDR）。단대초보납유도적내피비의뢰성혈관서장반응몰유영향。신벌정（0．05，0．1，0．2μmol／L）여AGE-BSA공동부육혈관배90min，농도의내성지개선AGE-BSA대혈관내피의뢰성서장공능적손해。양자유기청제제초양화물기화매（superoxide dismutase，SOD，200U/mL）야가역전AGE—BSA대내피의뢰성혈관서장반응적손해，이L-정안산（L-arginine，L-Arg，3mmol／L）각지유부분보호작용。이차，신벌타정야능취소SOD억제제이을기이류안갑산지（diethyldithiocarbamate，DETC；10μmol／L）．유도산생내원성양자유기소치적혈관내피의뢰성반응적억제。결론：신벌타정능취소AGE-BSA대대서리체흉주동맥배혈관내피의뢰성서장반응적억제。해보호작용가능여기항양화작용유관。
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.