糖基化终末产物对巨噬细胞基质金属蛋白酶9活性的影响以及辛伐他汀的干预作用
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The Effect of Advanced Glycation End Products on Macrophage Matrix Metalloproteinase-9 Activity and the Intervention Effect of Simvastatin
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    摘要:

    目的研究糖基化牛血清白蛋白对巨噬细胞的活化与基质金属蛋白酶9活性的影响,并观察辛伐他汀的干预效应。方法体外培养小鼠腹腔巨噬细胞,与不同浓度糖基化牛血清白蛋白、辛伐他汀共同培养,采用明胶酶谱法测定基质金属蛋白酶9活性。结果糖基化牛血清白蛋白可在体外诱发小鼠腹腔巨噬细胞形态变化。不同浓度的糖基化牛血清白蛋白(0、50、100、200、400mg/L)作用48h后,细胞培养基中基质金属蛋白酶9活性明显增强,且均明显高于对照组(n=5,p<0.05),呈剂量依赖效应。400mg/L糖基化牛血清白蛋白处理小鼠腹腔巨噬细胞不同时间后,作用12h时基质金属蛋白酶9活性与对照组比差异无显著性(n=5,p<0.05),作用24、36、48h时基质金属蛋白酶9活性均明显高于对照组,呈时间依赖效应(n=5,p<0.05)。加入辛伐他汀后,基质金属蛋白酶9活性明显降低。结论糖基化牛血清白蛋白可在体外活化巨噬细胞,使基质金属蛋白酶9活性增加,提示其致动脉粥样硬化及斑块破裂作用;辛伐他汀可明显降低基质金属蛋白酶9活性,说明其治疗作用的多向性。

    Abstract:

    Aim To investigate the effect of advanced glycation end product bovine serum albumin (AGE-BSA)on macrophage matrix metalloproteinase-9 (MMP-9) activity and the effects of Simvastatin. Methods Mouse peritoneal macrophages were incubated with AGE-BSA and Simvastain at different levels. MMP-9 activity was determined by Gelatin Zymography. Results AGE-BSA induced morphological changes of macrophage in vitro. After treatment with AGE-BSA (0, 50, 100, 200, 400 mg/L)for 48 hours, macrophage MMP-9 was significantly increased in contrast to the control, showing the dose-dependent effect (n=5, p<0.05). After treatment with 400 mg/L AGE-BSA for different duration, MMP-9 activity showed no significant difference at the time point of 12 hour (n=5, p<0.05), but MMP-9 activity was significantly increased in contrast to the control at the time point of 24, 36 and 48 hour, showing the time dependent effect (n=5, p<0.05). Simvastain decreased MMP-9 activity significantly. Conclusion AGE-BSA can activate macrophages in vitro and enhance MMP-9 activity, indicating its effect of atherogenesis and plaque rupture. Simvastatin can lower MMP-9 activity, showing statins' pleiotropic effects.

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李永军,刘政操,杨向红,王跃中,张亚加.糖基化终末产物对巨噬细胞基质金属蛋白酶9活性的影响以及辛伐他汀的干预作用[J].中国动脉硬化杂志,2006,14(9):789~791.

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  • 收稿日期:2005-11-23
  • 最后修改日期:2006-09-15
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