BQ-123在动脉粥样硬化中的抗炎效应  

Anti-inflammatory effect of BQ-123 in atherosclerosis

作　　者：李月华[1] 冯月英[1] 徐琛华[1] 刘晓红[1] 姜坚[1] 陈书艳[1] 

机构地区：[1]上海交通大学医学院新华医院心内科,上海200092

出　　处：《上海交通大学学报（医学版）》2009年第1期54-57,共4页Journal of Shanghai Jiao tong University:Medical Science

摘　　要：目的观察内皮素A(ETA)受体拮抗剂BQ-123在家兔动脉粥样硬化(AS)中的抗炎效应。方法32只雄性新西兰大白兔随机分成4组(n=8),对照组饲喂普通饲料10周;模型组、辛伐他汀组和BQ-123组均饲喂高脂饲料10周。采用ELISA法检测耳中动脉血清中前列腺素E2(PGE2)和ET-1水平;免疫组化SP法检测主动脉组织ET-1、巨噬细胞和COX-2蛋白表达。结果①分组饲喂10周后,模型组、辛伐他汀组和BQ-123组血清ET-1和PGE2水平均较对照组明显升高(P<0.01);但辛伐他汀组和BQ-123组均较模型组明显降低(P<0.05,P<0.01);AS兔血清中ET-1与PGE2水平成正相关(r=0.57,P<0.01)。②辛伐他汀组和BQ-123组AS斑块ET-1、巨噬细胞源泡沫细胞、COX-2蛋白阳性表达均较模型组明显降低(P<0.05或P<0.01),而BQ-123组又较辛伐他汀组进一步降低(P>0.05)。结论ET-1通过激活ETA受体可以导致家兔AS斑块COX-2表达上调和PGE2生成增多,选择性ETA受体拮抗剂BQ-123在家兔AS中具有抗炎效应。Objective To observe the anti-inflammatory effect of endothelin receptor A （ETA） antagonist BQ-123 in rabbits with atherosclerosis. Methods Tirty-two male New Zealand white rabbits were randomly divided into 4 groups： control, model, simvastatin, and BQ-123 treatment groups （n = 8）. Rabbits in control group were fed with standard diet for 10 weeks, and the other rabbits were fed with high-fat diet for 10 weeks. Peripheral blood of the rabbits was collected from ear artery for determination of the levels of endothelin-1 （ ET-1 ） and prostaglandin E2 （ PGE2 ） in serum with ELISA. SP immunohistochemical staining was used to detect the expressions of ET-1, macrophage and COX-2 protein in the aorta. Results （1） After 10-week feeding, the levels of ET-1 and PGE2 in serum in model, simvastatin, and BQ-123 groups were significantly higher than those in control group （P 〈 0.01 ）. However, those in simvastatin and BQ-123 groups were significantly lower than those in model group （ P 〈 0. 05, P 〈 0.01 ）. The level of ET-1 in rabbits with atherosclerosis was related to that of PGE2 （r = 0.57, P 〈0.01 ）. （2）Compared with model group, the positive expressions of ET-1, macrophage-derived foam cells and COX-2 protein in simvastatin and BQ-123 groups were significantly lower （P 〈 0.05, P 〈0.01）, and the positive expressions in BQ-123 group bad a further decrease compared with simvastatin group （P 〉 0.05）. Conclusion ETA activated by ET-1 up-regulates the expression of COX-2 protein and production of PGE2 in plaque in rabbits with atherosclerosis. Selective ETA antagonist BQ-123 has potent anti-inflammatory effect in rabbits with atherosclerosis.

关 键 词：选择性ETA受体拮抗剂 PGE2 ET-1 动脉粥样硬化 炎症 

分 类 号：R543[医药卫生—心血管疾病]