Cariporide对晚期氧化蛋白产物损伤血管内皮功能的保护作用  

Protective Effects of Cariporide on Endothelial Dysfunction Induced by Advanced Oxidation Protein Products in Rat Thoracic Aorta

作　　者：李先霞[1] 陈双秀[1] 曹维[2] 

机构地区：[1]岳阳职业技术学院药学与检验系,湖南省岳阳市414000 [2]中山大学药物开发中心,广东省广州市510080

出　　处：《中国动脉硬化杂志》2008年第2期125-128,共4页Chinese Journal of Arteriosclerosis

摘　　要：目的研究晚期氧化蛋白产物在体外能否直接损伤大鼠离体胸主动脉的内皮功能，及观察Caripofide对晚期氧化蛋白产物诱导的血管内皮损伤是否具有保护作用并探讨其可能的机制。方法雄性SD大鼠在戊巴比妥麻醉下，开胸切取胸主动脉，制成3～4min血管环备用，按文献方法制备晚期氧化蛋白产物。用不同浓度晚期氧化蛋白产物（1、2和3mmol／L）和Cariporide孵育大鼠离体胸主动脉环，分别检测乙酰胆碱引起的内皮依赖性舒张反应和硝普钠引起的非内皮依赖性舒张反应。并测定血管组织中超氧化物歧化酶的活性、丙二醛及一氧化氮的含量。结果晚期氧化蛋白产物能损伤乙酰胆碱诱导的内皮依赖性舒张反应，且血管组织丙二醛含量增加，超氧化物歧化酶活性下降，一氧化氮释放减少。Caripofide（0．01～1μmol／L）与晚期氧化蛋白产物（3mmol／L）共同孵育血管环90min，能改善晚期氧化蛋白产物对血管内皮依赖性舒张反应的损害，丙二醛含量减少，超氧化物歧化酶活性升高，一氧化氮释放增加。结论Caripofide对晚期氧化蛋白产物所致血管内皮依赖性舒张反应的损害具有明显保护作用，其机制可能与抗氧化作用和促进一氧化氮的合成或释放有关。Aim To explore whether Cariporide exerts beneficial effect on impaired vascular endothelial function elicited by exogenous advanced oxidation protein products （ AOPP）, and to investigate the potential mechanisms. Methods Male SD rats were killed by exsanguinafion after anesthesia with pentobarbital sodium （30 mg/kg, IP）. The thoracic aorta was immediately isolated and was cut into 3 ～ 4 mm rings. AOPP was prepared according to the methods of article. Rat aortic isolated rings were incubated with AOPP （1, 2, 3 mmol/L） and Cariporide （0.01 ～ 1 μmol/L） for 90 rain. Endothelimn-dependent relaxation （ EDR） induced by acetylcholine （ Ach）, endothelium-independent relaxation induced by sodium nitroprusside （ SNP）, superoxide dismutase （SOD） activity, malondialdehyde （MDA） and nitric oxide （NO） were measured in rat isolated aorta. Results Co-incubation of aortic rings with AOPP-BSA （3 mmol/L） for 90 min resulted in a significant inhibition of EDR response to Ach. Cariporide （0.01～ 1 μmol/L） groups were significantly attenuated the inhibition of EDR reponse induced by AOPP-BSA. Conclusion Cariporide was abie to protect against vascular endothelial dysfunction caused by AOPP-BSA. The mechanisms may be involved in antioxidative stress and increasing the synthesization and release of NO.

关 键 词：药理学 CARIPORIDE 晚期氧化蛋白产物 内皮依赖性舒张 氧化应激 超氧化物歧化酶 

分 类 号：R96[医药卫生—药理学]