氯沙坦对球囊成形术后血管内膜增生影响的实验研究

目的研究氯沙坦抗氧化应激及对球囊成形术后血管内膜增生及核因子κB活性的影响。方法采用内皮剥脱后高脂饮食（含1．5％胆固醇）喂养制作兔腹主动脉粥样硬化模型,然后对狭窄部位行球囊成形术。术后氯沙坦组给予氯沙坦10mg／（kg·d）口服,对照组只喂生理盐水,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、增殖细胞核抗原、细胞间粘附分子1的表达。结果与对照组相比,氯沙坦组内膜厚度／中膜厚度比值、内膜面积／中膜面积比值均显著减少（P〈0．01）。核因子κB及其靶基因产物细胞间粘附分子1水平、细胞增值核抗原亦因氯沙坦的干预而明显减少（P〈0．01、P〈0．05、P〈0．01）。结论氯沙坦通过抑制氧化应激,减少活性氧族生成,抑制平滑肌细胞迁移、增殖和新生内膜形成,减轻再狭窄。

Experimental Study of Losartan on Neointimal Prollferation after Halloon Angioplasty

Objective To investigate the effect of losartan on neointimal proliferation and expression of nuclear factor-κB （NF-κB） via suppression of oxidative stress. Methods White rabbits were fed with a 1.5% cholesterol diet for 8 weeks after undergoing endothelial denudation. The model of abdominal aortic atherosclerosis was constructed and balloon angioplasty was performed on the injured arteries. Rabbits of losartan group were orally administered with losartan [ 10 mg/（kg·d）], while rabbits of control group were given normal saline. Four weeks after angioplasty tissue morphology of artery segments were observed. Proliferating ceil nuclear antigen （PCNA）, NF-κB and intracellular adhesive molecule-1 （ICAM-1） were investigated by immunohistochemistry analysis. Results Compared with the control group, the intimal thickness （IT）, intimal area （IA）, the ratio of IT to medial thickness （MT） and ratio of IA to medial area （MA） of the losartan group were significantly redced （P〈0. 01 ） . PCNA in the neointima and the expression of NF-κB and ICAM-1 significantly decreased respectively in the losartan group （P〈0. 01, P〈0. 01 and P〈0. 05）. Conclusion Losartan could significantly reduce the formation of reactive oxygen species, inhibit the migration and proliferation of smooth muscle cells as well as formation of neointima via suppression of oxidative stress and mitigate restenosis after balloon angioplasty.