氯沙坦干预早期动脉粥样硬化家兔内膜增生的相关因素  

Related factors of losartan intervention on intimal proliferation of rabbit model with early atherosclerosis

作　　者：李爱民[1] 何作云[1] 覃军[1] 周小波[1] 耿建萌[1] 

机构地区：[1]解放军第三军医大学新桥医院心内科,重庆市400037

出　　处：《中国临床康复》2004年第18期3491-3493,共3页Chinese Journal of Clinical Rehabilitation

摘　　要：目的:探讨血管紧张素II受体拮抗剂氯沙坦对加速性动脉粥样硬化(atherosclerosis,AS)早期家兔血管单核细胞趋化蛋白-1(monocytechemoattractantprotein-1,MCP-1)及丝裂素活化蛋白激酶(mitogen-activatedproteinkinases,MAPK)蛋白表达的影响。方法:以家兔加速性动脉粥样硬化早期模型为研究对象,将24只家兔随机分成对照组、早期动脉粥样硬化组和氯沙坦干预组,每组8只,采用组织学、免疫细胞化学和生物化学方法评价加速性AS早期家兔血管组织学、增殖细胞核抗原(proliferatingcellnuclearantigen,PCNA)、MAPK和MCP-1蛋白表达和组织胆固醇含量的改变。结果:早期动脉粥样硬化组血管内膜与中膜厚度比值、内膜PCNA阳性细胞数明显增加,MAPK与MCP-1蛋白表达平均光密度值均显著增加(P<0.001),氯沙坦干预组内膜与中膜厚度比值较早期动脉粥样硬化组显著下降(0.92±0.10和0.23±0.04,t=30.086,P<0.001),PC-NA阳性细胞数明显减少(t=23.944,P<0.001),血管壁MAPK与MCP-1蛋白表达水平明显下降(0.025±0.006和0.054±0.007,0.057±0.006和0.205±0.019,F=265.14,410.55,P<0.001),主动脉组织胆固醇含量明显降低(t=3.913,P<0.05)。结论:氯沙坦干预可抑制血管损伤时MCP-1及MAPK蛋白表达,减轻加速性AS病变血管内膜增生。AIM:To explore the effects of losartan(angiotensin II receptor antagnosit) on the expression of mitogen activated protein kinases(MAPK) and monocyte chemoattractant protein 1(MCP 1) in a rabbit model of early accelerated atherosclerosis(AS). METHODS:Twenty four Japanese male rabbits were randomly divided into contro,early accelerated AS and losartan treated groups of 8 rabbits each.Methods of histology,immunohistochemistry and biochemistry were used to evaluate the vascular histology,proliferating cell nuclear antigen(PCNA),MAPK and MCP 1 protein expression and the changes of cholesterol level. RESULTS:The ratio of vascular intimal to medial thickness,and the number of PCNA cells were increased obviously,and mean absorbance(A) values of MAPK and MCP 1 protein expression were significant increased in the AS group(P< 0.001).The ratio of vascular intimal to medial thickness in the losartan treated group(0.92±0.10) was decreased significantly as compared with the AS group(0.23±0.04)(t=30.086,P< 0.001),and the number of positive PCNA cells was reduced obviously as well as the mean A values of MAPK and MCP 1 protein expression(0.025±0.006 and 0.054±0.007,0.057±0.006 and 0.205±0.019)(F=265.14,410.55,P< 0.001).Aortic cholesterol content in the losartan treated group was significantly decreased as compared with that in the AS group(t=3.913,P< 0.05). CONCLUSION:Losartan can inhibit MAPK and MCP 1 protein expression of injured vessels,relieve intimal proliferation and decrease cholesterol deposit in vascular walls of accelerated AS,and thereby may play an important role in the prevention of AS.

关 键 词：动脉粥样硬化 单核细胞化学吸引蛋白质类 蛋白激酶类 抗高血压药 兔 

分 类 号：R543.1[医药卫生—心血管疾病]