罗格列酮对急性冠状动脉综合征患者外周血单核细胞源性巨噬细胞表达基质金属蛋白酶9和组织型基质金属蛋白酶抑制剂1的影响
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深圳市科技基金项目(JH200507120929A);龙岗区科技基金项目(200514)


Impact of Rosiglitazone on the Expression of Matrix Metalloproteinases-9 and Tissue Inhibitor of Metalloproteinase-1 of Peripheral Blood Mononuclear Cell-Derived Macrophage in Patients with Acute Coronary Syndrome
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    摘要:

    目的探讨过氧化体增殖物激活型受体γ在调节急性冠状动脉综合征患者外周血单核细胞源性巨噬细胞表达基质金属蛋白酶9、组织型基质金属蛋白酶抑制剂1中的作用。方法用不同浓度罗格列酮干预急性冠状动脉综合征患者和对照者单核细胞源性巨噬细胞,然后测定各组上清液中基质金属蛋白酶9、组织型基质金属蛋白酶抑制剂1浓度及单核细胞源性巨噬细胞过氧化体增殖物激活型受体γ、基质金属蛋白酶9和组织型基质金属蛋白酶抑制剂1mRNA的表达。结果干预后,急性冠状动脉综合征组及对照组过氧化体增殖物激活型受体γmRNA表达上调,表达强度与罗格列酮浓度呈正变关系;基质金属蛋白酶9表达下调,在急性冠状动脉综合征组其下调程度与罗格列酮浓度呈反变关系;组织型基质金属蛋白酶抑制剂1的表达无明显变化。结论罗格列酮干预可上调单核细胞源性巨噬细胞过氧化体增殖物激活型受体γ表达,下调基质金属蛋白酶9表达,在急性冠状动脉综合征组尤其明显,对组织型基质金属蛋白酶抑制剂1表达无明显影响;可能存在稳定动脉粥样斑块的作用。

    Abstract:

    Aim To investigate the role of peroxisome proliferator activated receptor-γ (PPAR-γ) in the regulation of matrix metalloproteinases (MMP-9) and tissue inhibitor of metalloproteinase (TIMP-1) expression by peripheral blood monocyte derived macrophages (MDM) in acute coronary syndrome (ACS) patients. Methods MDM were from patients with ACS and controls have been assigned to different subgroups and incubated by different concentrations of rosiglitazone. The concentrations of MMP-9 and TIMP-1 in the supernate of MDM and the expression strength of PPAR-γ,MMP-9 and TIMP-1 mRNA in MDM were analysed and compared between ACS group and control group,and among the different concentrations of rosiglitazone intervention subgroups. Results After rosiglitazone interventing,either in ACS group or in control group,PPAR-γ mRNA expression were significantly upward,and there were a positive correlation between the expression strength and rosiglitazone intervention concentration; both the MMP-9 concentration in the supernate and the expression strength of MMP-9 mRNA were descended,and there were negative correlation between the extent of its descent in the ACS group and rosiglitazone concentration. There was no significant change in TIMP-1 concentration in the supernate of MDM and TIMP-1mRNA expression after rosiglitazone interventing. Conclusion MDM had endogenous PPAR-γ receptor,and it could be activated by rosiglitazone. Rosiglitazone intervention significantly increased the expression of PPAR-γ of MDM,reduced the expression of MMP-9,particularly in the ACS group. TIMP-1 expression was not affected. There may be impact of stablizing atherosclerotic plaque.

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罗玉梅,万新红,姜德谦,郭洪波,陈朝霞,王合金.罗格列酮对急性冠状动脉综合征患者外周血单核细胞源性巨噬细胞表达基质金属蛋白酶9和组织型基质金属蛋白酶抑制剂1的影响[J].中国动脉硬化杂志,2009,17(2):132~136.

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  • 收稿日期:2008-09-22
  • 最后修改日期:2009-01-04
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