普罗布考对巨噬细胞分泌基质金属蛋白酶9的抑制作用
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国家973项目(G2000056905);国家自然科学基金项目(30171084)资助


Probucol Reduces Matrix Metalloproteinase-9 Secretion of THP-1 Monocyte-Derived Macrophages Induced by Oxidized Low Density Lipoprotein
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    摘要:

    通过观察普罗布考对THP 1细胞基质金属蛋白酶9表达的影响,初步探讨普罗布考稳定斑块的分子机制。运用逆转录聚合酶链反应、免疫印迹、明胶酶图等方法,检测氧化型低密度脂蛋白诱导后的人单核细胞 巨噬细胞系THP 1细胞基质金属蛋白酶9mRNA表达、蛋白分泌和酶活性。实验发现,在氧化型低密度脂蛋白(80mg L)刺激下,THP 1细胞基质金属蛋白酶9的表达和酶活性明显增强;予普罗布考2 0、4 0、6 0 μmol L处理,均能在对细胞活性无影响的前提下,显著抑制基质金属蛋白酶9的蛋白分泌量及明胶降解活性,且这种作用呈浓度依赖性增强,其中6 0 μmol L的普罗布考抑制基质金属蛋白酶9的蛋白分泌和明胶降解活性分别达74 .0 %±2 .4 %和4 8.0 %±5 .1% (P<0 .0 5 )。实验结果说明,普罗布考能有效抑制巨噬细胞的基质金属蛋白酶9的蛋白分泌及其活性,这一作用可能是其抗动脉粥样硬化和稳定斑块的重要机制之一。

    Abstract:

    Aim To investigate the underlying molecular mechanism of probucol stabilizing plaque and preventing acute coronary syndromes. Methods Reverse transcription polymerase chain reaction (RT PCR), Western blot and gelatin zymography were performed to detect matrix metalloproteinase 9 (MMP 9) expression,secretion and activity in THP 1 monocyte derived macrophages induced by oxidized low density lipoprotein (ox LDL). Results The expression and enzyme activity of MMP 9 significantly increased in THP 1 monocyte derived macrophages exposed to ox LDL (80 mg/L) for 12 h. Probucol at a concentration of 20, 40 and 60 μmol/L inhibited MMP 9 protein secretion by 27.0%±2.6%,45.0%±5.5% and 74.0%± 2.4% respectively (p<0.05), and decreased enzyme activities by 29.0%±3.2%,34.0%±1.9% and 48.0%±5.1% respectively (p<0.05), but had no influence on MMP 9 mRNA expression. Conclusion Probucol can effectively inhibit MMP 9 secretion in macrophages, which may play an important role in stabilizing plaque and anti atherosclerosis.

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严鹏科,廖端芳,杨永宗.普罗布考对巨噬细胞分泌基质金属蛋白酶9的抑制作用[J].中国动脉硬化杂志,2003,11(3):199~202.

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  • 收稿日期:2002-08-02
  • 最后修改日期:2003-02-25
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