洛伐他汀抑制人脐静脉内皮细胞基质金属蛋白酶9表达和活性
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国家自然科学基金项目(81070221)及湖南省卫生厅项目(B2011-054)资助


Lovastatin Inhibits Matrix Metalloproteinase-9 Expression and Activity of Human Umbilical Vein Endothelial Cells
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    摘要:

    目的观察洛伐他汀对人脐静脉内皮细胞基质金属蛋白酶9表达的影响。方法体外培养人脐静脉内皮细胞,加入20 μg/L肿瘤坏死因子α诱导后,再用0.05~1.35 μmol/L洛伐他汀处理0~24 h,蛋白印迹以及逆转录聚合酶链反应分别检测基质金属蛋白酶9的蛋白和mRNA表达情况,明胶酶谱法测定基质金属蛋白酶9活性。结果肿瘤坏死因子α能诱导人脐静脉内皮细胞的基质金属蛋白酶9表达和活性增强,洛伐他汀处理后,基质金属蛋白酶9的mRNA水平、蛋白量及活性均降低,且呈明显的时间和剂量依赖性,其中0.05 μmol/L洛伐他汀能显著降低基质金属蛋白酶9的mRNA水平,但在蛋白水平和基质金属蛋白酶9活性上,0.05 μmol/L洛伐他汀并没有表现出显著的降低效果,其余洛伐他汀各浓度均能对基质金属蛋白酶9的mRNA水平、蛋白量及活性产生显著的抑制作用,以1.35 μmol/L洛伐他汀的抑制效果最显著。结论洛伐他汀能抑制肿瘤坏死因子α诱导的人脐静脉内皮细胞基质金属蛋白酶9的表达。

    Abstract:

    AimTo study the effect of lovastatin on expression and activity of matrix metalloproteinase-9 (MMP-9) in a human umbilical vein endothelial cells (HUVECs) line.MethodsCultured HUVECs were stimulated by 20 μg/L tumor necrosis factor-alpha (TNF-α), and then incubated with 0.05-1.35 μmol/L of lovastatin for 0-24 h.The protein and mRNA level were detected by Western blotting and reverse transcription polymerase chain reaction (RT-PCR) respectively, and the activity of MMP-9 was analyzed by gelatin zymography.ResultsMMP-9 expression was induced by TNF-α in HUVECs, lovastatin attenuated both expression and activity of MMP-9 in a time and dose-dependent manner.0.05 μmol/L lovastatin inhibited MMP-9 expression in mRNA level, but not in protein level, but activity of MMP-9 cannot be inhibited by 0.05 μmol/L lovastatin.Other concentration of lovastatin groups can inhibit MMP-9 expression both in mRNA and protein levels, including activity of MMP-9, the maximum inhibitory effect was induced by 1.35 μmol/L lovastatin.ConclusionExpression and activity of MMP-9 can be inhibited by lovastatin in HUVECs.

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曾钧发,王佐,罗勇,雷建军,桂培根.洛伐他汀抑制人脐静脉内皮细胞基质金属蛋白酶9表达和活性[J].中国动脉硬化杂志,2012,20(3):217~220.

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  • 收稿日期:2011-10-25
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