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抗骨桥蛋白抗体抑制血管内膜增生的实验研究 被引量:9

Experimental study on inhibition of restenosis by anti-osteopontin antibody after de-endothelium
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摘要 目的:探讨抗骨桥蛋白(OPN)抗体对大鼠血管内皮剥脱术后内膜增生的抑制效果及其机制。方法:利用球囊导管建立大鼠颈总动脉-主动脉血管内皮剥脱模型,通过尾静脉注射兔抗鼠OPN多克隆抗体后,利用明胶酶图分析、Westernblotting、免疫组织化学等方法观察血管内膜厚度、基质转换酶类和粘附分子表达活性。结果:血管内膜剥脱大鼠给予抗OPN抗体后,血管内膜的增生受到明显抑制,内膜与中膜面积之比(I/M)降低(P<0.05),管腔狭窄程度减轻。血管壁MMP-2和TIMP-2的表达量无明显变化但MMP-2活性显著下降(P<0.05)。而且,抗OPN抗体对血管新生内膜的OPN表达水平也无明显影响。结论:抗OPN抗体通过阻断骨桥蛋白功能,减缓细胞外基质降解而有效抑制血管内膜增生。 AIM: To investigate the mechanism of inhibiting the neointimal formation through blocking osteopontin (OPN) by using anti - OPN antibody. METHODS: The anti - OPN antibody was injected via tail vein after the left carotid artery of rats was de - endothelialized by balloon catheter. The expression of matrix metalloproteinase - 2 ( MMP - 2), tissue inhibitor of matrix metalloproteinase- 2 (TIMP- 2) and OPN were detected by gelatin zymogram, Western blotting, immunohistochemistry and flow cylometry. RESULTS: The neointima in rats treated with anti - OPN antibody was significantly thinner than that in untreated rats (P 〈0.05). The intimal/medial area (I/M) declined in the treatment group, compared with the untreated rats. In addition, MMP- 2 activity in neointima' was significantly inhibited, but the expression of MMP - 2, TIMP- 2 and OPN were unchanged in rat treated with anti - OPN antibody. CONCLUSION: Anti - OPN antibody can inhibit the intima hyperplasia by blocking the OPN function and inhibiting the MMP - 2 activity.
出处 《中国病理生理杂志》 CAS CSCD 北大核心 2006年第3期477-480,共4页 Chinese Journal of Pathophysiology
基金 国家科技部科技攻关计划课题(No.2002BA755C) 河北省重大科技攻关计划课题(No.02276405D)
关键词 骨桥蛋白 抗体 血管内膜 增生 Osteopontin Antibodies Tunica intima Hyperplasia
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