CAJ | 학술논문

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10 mg/(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＜0.01).氯沙坦组新生内膜中巨噬细胞、平滑肌细胞数均明显少于对照组(P＜0.01,0.05).氯沙坦组兔血管核因子κB及其靶基因产物细胞间黏附分子1的水平也明显低于对照组(P＜0.01,0.05).结论:氯沙坦可阻断血管紧张素Ⅱ受体,进而抑制核因子κB,从而抑制平滑肌细胞迁移、增殖和新生内膜形成.
배경:핵인자κB가삼여세포증식반응,기복잡적궤제수심입연구.목적:연구록사탄대혈관내막증생급핵인자κB활성적영향.설계:이실험동물위연구대상,완전수궤분조설계,탐색성실험연구.단위:일소대학의원심내과.대상:본실험우2001-11/2002-06재무한대학인민의원실험실급실험동물중심완성.실험선용웅성일본대이백토24지,수궤취8지작위정상조,시종사이보통사료;령외16지조성복주동맥내피손상병이고지음식사양8주후재수궤분위대조조、록사탄조,매조8지.방법:술후록사탄조급여록사탄10 mg/(kg·d)구복,대조조위생리염수.4주후취복주동맥행조직형태학관찰급용면역조직화학방법분석핵인자κB、α-평활기기동단백、거서세포、세포간점부분자1.주요관찰지표:3조동물경불동간예조시후혈관내막후도、내막면적、내막핵인자κB,세포간점부분자1적표체화평활기세포、거서세포수량비교.결과:대조조토혈관록사탄조혈관내막후도、내막후도/중막후도、내막면적、내막면적/중막면적명현대우정상조(P＜0.01).록사탄조토혈관내막후도、내막후도/중막후도、내막면적、내막면적/중막면적[(0.42±0.08)mm,0.43±0.10,(3.18±0 83)mm2,0.54±0.11]균명현소우대조조[(1.35±0.35)mm,0.67±0.15,(5.30±1.71)mm2,0.77±0.14](P균＜0.01).록사탄조신생내막중거서세포、평활기세포수균명현소우대조조(P＜0.01,0.05).록사탄조토혈관핵인자κB급기파기인산물세포간점부분자1적수평야명현저우대조조(P＜0.01,0.05).결론:록사탄가조단혈관긴장소Ⅱ수체,진이억제핵인자κB,종이억제평활기세포천이、증식화신생내막형성.
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.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 Ⅱ receptor and inhibits NF-κB, thus inhibiting migration and proliferation of SMCs and formation of neointima.