阻断清道夫受体A对巨噬细胞源泡沫细胞基质金属蛋白酶及其组织抑制剂表达的影响
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国家自然科学基金(39900061)资助


Effects of Blocking Scavenger Receptor Aon Expression of Matix Metalloproteinase and its Tissue Inhibitor of Metalloproteinase in Macrophage-Drived Foam Cells
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    摘要:

    为探讨巨噬细胞源泡沫细胞基质金属蛋白酶及其组织抑制剂的表达及活性与清道夫受体A的关系,应用油红O染色、高效液相色谱法检测巨噬细胞的泡沫化,逆转录聚合酶链反应检测细胞清道夫受体A的表达,Westernblot、明胶酶谱法观测巨噬细胞泡沫化后阻断清道夫受体A对THP 1细胞基质金属蛋白酶2、基质金属蛋白酶9、组织型基质金属蛋白酶抑制剂1及组织型基质金属蛋白酶抑制剂2表达的影响。结果发现,THP 1细胞在佛波酯处理2 4h后有清道夫受体A的表达,清道夫受体A反义寡核苷酸及其抗体能显著降低基质金属蛋白酶2和基质金属蛋白酶9的蛋白表达和活性,并增加组织型基质金属蛋白酶抑制剂1和组织型基质金属蛋白酶抑制剂2的表达。结果提示,阻断清道夫受体A有助于基质金属蛋白酶与组织型基质金属蛋白酶抑制剂的平衡维持,从而抑制细胞外基质的降解

    Abstract:

    Aim To investigate the effects of the scavenger receptor A( SR A) on expression of matrix metalloproteinase 2 (MMP 2) and matrix metalloproteinase 9 (MMP 9) and its tissue inhibitor of metalloproteinase (TIMP) in macrophage drived foam cells. Methods THP 1 cells were incubated with PMA, then added oxidized low density lipoprotein (ox LDL) to induce macrophage cell foaming. Foamed macrophage cells were verified by oil red staining and high performance liquid chromatography (HPLC). Scavenger receptor A mRNA was detected by reverse transcriptase polymerase chain reaction (RT PCR). Antisense and antibody were used to block SR Ain foamed cell. MMP 2, MMP 9, TIMP 1 and TIMP 2 were detected by Western blot. MMP 2 and MMP 9 activities in media were estimated using zymography. Results Blocking SR Ainhibits activities and expression of MMP 2 and MMP 9, increases the expression of TIMP 1 and TIMP 2. Conclusions Blocking the activities of SR Amay contribute to maintain the balance between MMP and TIMP and inhibit macrophage mediated matrix breakdown in the atherosclerotic plaques.

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危当恒,万腊香,刘录山,万载阳,杨永宗.阻断清道夫受体A对巨噬细胞源泡沫细胞基质金属蛋白酶及其组织抑制剂表达的影响[J].中国动脉硬化杂志,2003,11(2):111~113.

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  • 收稿日期:2002-09-16
  • 最后修改日期:2003-03-06
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