兔血管内膜增生过程中核因子κB活性与氯沙坦的影响(英文)

Effect of losartan on activity of nuclear factor-kappa B in the process of rabbit intimal proliferation

背景:核因子κB可参与细胞增殖反应,其复杂的机制需深入研究。目的:研究氯沙坦对血管内膜增生及核因子κB活性的影响。设计:以实验动物为研究对象,完全随机分组设计,探索性实验研究。单位:一所大学医院心内科。对象:本实验于2001-11/2002-06在武汉大学人民医院实验室及实验动物中心完成。实验选用雄性日本大耳白兔24只,随机取8只作为正常组,始终饲以普通饲料;另外16只造成腹主动脉内皮损伤并以高脂饮食饲养8周后再随机分为对照组、氯沙坦组,每组8只。方法:术后氯沙坦组给予氯沙坦10mg/(kg·d)口服,对照组喂生理盐水。4周后取腹主动脉行组织形态学观察及用免疫组织化学方法分析核因子κB、α-平滑肌肌动蛋白、巨噬细胞、细胞间黏附分子1。主要观察指标:3组动物经不同干预措施后血管内膜厚度、内膜面积、内膜核因子κB,细胞间黏附分子1的表达和平滑肌细胞、巨噬细胞数量比较。结果:对照组兔血管氯沙坦组血管内膜厚度、内膜厚度/中膜厚度、内膜面积、内膜面积/中膜面积明显大于正常组(P<0.01)。氯沙坦组兔血管内膜厚度、内膜厚度/中膜厚度、内膜面积、内膜面积/中膜面积(0.42±0.08)mm,0.43±0.10,(3.18±0.83)mm2,0.54±0.11均明显小于对照组(1.35±0.35)mm,0.67±0.15,(5.30±1.71)mm2,0.77±0.14(P均<0.

BACKGROUND:Nuclear factor-kappa B(NF-κB) participates in cellular proliferation,but its complex mechanism needs to be further investigated. OBJECTIVE:To investigate the effect of losartan on neointimal proliferation and NF-κB activation. DESIGN:Completely random grouping design and exploratory experimental research based on the experimental animals. SETTING:Department of cardiology in a university-affiliated hospital. PARTICIPANTS:This experiment was conducted at the Experimental Animal Center and Cardiovascular Laboratory of Renmin Hospital of Wuhan University between November 2001 and June 2002.Eight out of 24 male Japanese white rabbits were randomly assigned to normal group,receiving normal feed until being sacrificed;the other 16 rabbits underwent abdominal aorta balloon de-endothelialization and then were placed on a high-cholesterol diet for 8 weeks,during which time they were subdivided into two groups:losartan group and control group,8 in each one. METHODS:After de-endothelialization,10 mg/(kg·d) losartan was orally administered to the rabbits in losartan group,while the rabbits in control group were given normal saline.Four weeks later,excised artery segments were prepared for histomorphometric observation and κ-smooth muscle actin,macrophage,nuclear factor-κB(NF-κB) and intracellular adhesive molecule-1(ICAM-1) immunohistochemical analysis. MAIN OUTCOME MEASURES:Aortic intimal thickness,intimal area,expression of NF-κB,ICAM-1 in intima,number of smooth muscle cell(SMC) and macrophage in intima. RESULTS:The intimal thickness,intimal area,intimal/media thickness ratio and intimal/media ratio in control and losartan groups were much greater than those in normal group[(0.42±0.08) mm,(0.43±0.10),(3.18±0.83) mm2,and(0.54±0.11),respectively](P< 0.01).Those were much smaller in losartan group than in control group[(1.35±0.35) mm,(0.67±0.15),(5.30±1.71) mm2,(0.77±0.14)](all P< 0.01). Macrophages and smooth muscle cells in neointima in losartan group were much fewer than those in control group(P< 0.01,0.05).The level of NF-κB and ICAM-1 in losartan group was much lower than that in control group(P< 0.01,0.05). CONCLUSION:Losartan can block angiotensin Ⅱreceptor and inhibits NF-κB,thus inhibiting migration and proliferation of SMCs and formation of neointima.