洛伐他汀对血管平滑肌细胞基质金属蛋白酶3表达的影响
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Effect of Lovastatin on Secretion of Matrix Metalloproteinase-3 in Vascular Smooth Muscle Cells
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    摘要:

    观察洛伐他汀对兔血管平滑肌细胞基质金属蛋白酶3表达的影响及其作用机制。用Westernblot检测基质金属蛋白酶3蛋白水平,采用电泳迁移率变动分析法测定AP 1结合活性,用逆转录聚合酶链反应检测基质金属蛋白酶3mRNA水平。结果发现,白细胞介素1α和血小板源生长因子BB联合作用于兔血管平滑肌细胞,可明显增加基质金属蛋白酶3的表达,洛伐他汀抑制这种刺激作用,使基质金属蛋白酶3的表达减低,且呈浓度依赖性;该抑制作用可被甲羟戊酸和双香叶酯基焦磷酸盐所逆转,而不被角鲨烯所逆转。白细胞介素1α和血小板源生长因子BB联合作用后使兔血管平滑肌细胞AP 1结合活性和基质金属蛋白酶3mRNA水平明显增高,洛伐他汀抑制白细胞介素1α和血小板源生长因子BB上调AP 1结合活性的作用,但对基质金属蛋白酶3mRNA水平无明显影响。结果提示,洛伐他汀不依赖其调脂作用抑制血管平滑肌细胞基质金属蛋白酶3的生成,从而在理论上有抗动脉粥样硬化和增加斑块稳定性的作用

    Abstract:

    Aim To investigate the effect of lovastatin on secretion of matrix metalloproteinase 3 (MMP 3) in cultured vascular smooth muscle cells (VSMC) of rabbits. Methods Expression of MMP 3 was detected by Western blot, AP 1 binding activity was detected by electrophoretic mobility shift assay (EMSA), mRNA level of MMP 3 was detected by reverse transcription polymerase chain reaction (RT PCR). Results Interleukin 1α (IL 1α) combined with platelet derived growth factor BB (PDGF BB) strongly increased the expression of MMP 3 at VSMC. Lovastatin inhibited the upregulated expression of MMP 3 by IL 1α and PDGF BB in a concentration dependent manner. This inhibitory effect was reversed by mevalonate and GGPP, but not by squalene. Lovastatin decreased AP 1 binding activity enhanced by IL 1α and PDGF BB, but had no significant effect on MMP 3 mRNA level. Conclusion Lovastatin inhibited MMP 3 secretion at VSMC, which could contribute to its plaque stablising effects.

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栾朝霞,高沁怡,裴著果.洛伐他汀对血管平滑肌细胞基质金属蛋白酶3表达的影响[J].中国动脉硬化杂志,2003,11(4):339~341.

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  • 收稿日期:2002-10-08
  • 最后修改日期:2003-05-25
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