氯沙坦对球囊成形术后兔血管内膜增生及核因子κB活性的影响
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湖北省教委青年基金(99B010)部分资助


Effect of Losartan on Neointimal Proliferation and Activation of Nuclear Factor-kappa B After Balloon Angioplasty in Rabbits
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    摘要:

    为研究氯沙坦对球囊成形术后血管内膜增生及核因子κB活性的影响,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、α平滑肌肌动蛋白、巨噬细胞、细胞间粘附分子1的表达。结果发现,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 .0 1)。氯沙坦组新生内膜中巨噬细胞、平滑肌细胞数均较对照组显著减少(P<0 .0 1和P<0 .0 5 )。核因子κB及其靶基因产物细胞间粘附分子1水平亦因氯沙坦的干预而明显减少(P<0 .0 1和P<0 .0 5 )。结果提示,氯沙坦明显抑制球囊成形术后内膜增生,其机制可能为阻断血管紧张素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。

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    Aim To investigate the effect of losartan on neointimal proliferation and expression of nuclear factor κB(NF κB). Methods Japanese White rabbits underwent abdominal aorta balloon de endothelialization and then were treated with a 1.5% cholesterol diet for 8 weeks. Then balloon angioplasty was performed on the injured arteries. Immediately after balloon angioplasty, the rabbits of the losartan group was orally administered with losartan [10 mg/(kg·d)], while the rabbits of the control group were given normal saline. Animals were killed four weeks after angioplasty, and excised artery segments were prepared for histomorphological observation and α smooth muscle actin, macrophage, NF κB and intracellular adhesive molecule 1 (ICAM 1) were investigated by immunohistochemistry analysis. Results Losartan treatment significantly inhibited neointimal proliferation. Compared with the control group, the intimal thickness (IT), intimal area (IA), the ratio of IT/MT and IA/MA of the losartan group were significantly reduced (p<0.01). Also, macrophages and smooth muscle cells (SMC) in the neointima were significantly diminished (p<0.01 and p<0.05) and the expression of NF κB and ICAM 1 were respectively decreased in the losartan group (p<0.01 and p<0.05). Conclusions These findings suggest that losartan could significantly relieve neointimal proliferation after balloon angioplasty, possibly through inhibiting angiotensinⅡ and NF κB, thus inhibits inflammatory reaction, migration and proliferation of SMC as well as formation of neointima which contributes to restenosis after balloon angioplasty.

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刘颖,李建军,李庚山,张玉平,王晶,夏泠,徐红新.氯沙坦对球囊成形术后兔血管内膜增生及核因子κB活性的影响[J].中国动脉硬化杂志,2003,11(2):131~134.

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  • 收稿日期:2002-07-13
  • 最后修改日期:2003-03-06
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