氧化型低密度脂蛋白对人血单核细胞基质金属蛋白酶表达及活性的影响  

Effect of Oxidized Low Density Lipoprotein on the Expression and Activity of Matrix Metalloproteinases in Human Monocytes

作　　者：王长谦[1] 汤大鸣[1] 谢秀兰[1] 徐依敏[1] 丁弘毅[1] 王利民[1] 王彬尧[1] 黄定九[1] 

机构地区：[1]上海第二医科大学附属仁济医院心内科,上海市200001

出　　处：《中国动脉硬化杂志》2003年第2期126-130,共5页Chinese Journal of Arteriosclerosis

基　　金：上海市青年科技启明星计划 (98QB1 4 0 1 4 )资助

摘　　要：探讨氧化修饰低密度脂蛋白对人单核细胞源巨噬细胞基质金属蛋白酶的表达及其活性的影响。采用体外培养人单核细胞源巨噬细胞 ,分别应用逆转录聚合酶链式反应和蛋白印迹检测基质金属蛋白酶 2和基质金属蛋白酶 9基因和蛋白表达 ,酶谱法检测基质金属蛋白酶活性。结果发现 ,不同浓度 (10、2 0、4 0mg/L)氧化修饰低密度脂蛋白对人单核细胞源巨噬细胞基质金属蛋白酶 2和基质金属蛋白酶 9基因表达的影响均明显高于相应浓度低密度脂蛋白组 ;基质金属蛋白酶 2和基质金属蛋白酶 9蛋白表达也明显高于相应浓度低密度脂蛋白组 ;基质金属蛋白酶 2和基质金属蛋白酶 9的活性明显高于相应剂量低密度脂蛋白组 ,且随剂量增加而增高。提示氧化修饰低密度脂蛋白可刺激人单核细胞源巨噬细胞基质金属蛋白酶 2、基质金属蛋白酶 9基因及蛋白的表达 ,增强其活性 ,因而有可能促进动脉粥样硬化斑块内基质降解 ,形成易损斑块 。Aim To observe the effect of oxidized low density lipoprotein (ox LDL) on the expression and activity of matrix metalloproteinases(MMPs). Methods Human monocyte derived macrophages were cultured in vitro and the gene and protein expressions of MMPs (MMP 2 and MMP 9) were detected by reverse transcription polymerase chain reaction and Western blot respectively. MMPs'activity was detected by Zymography. Results The results revealed that 10,20 and 40 g/L of ox LDL could stimulate the gene expression of MMP 2 and MMP 9 in comparison with the same concentrations of LDL. The expressions of MMP 2 protein and MMP 9 protein were higher in ox LDL groups than in LDL groups. The activity of MMP 2 and MMP 9 was also significantly higher in different concentrations of ox LDL groups than the same concentrations of LDL groups. The activity of MMP 2 and MMP 9 was in a dose dependent manner in ox LDL group. Conclusions The results indicate that ox LDL can obviously increase the expressions and activities of MMP 2 and MMP 9 in human monocyte derived macrophages. So ox LDL could enhance the breakdown of matrix in lesions of atherosclerosis which could probably induce vulnerable plaque. Rupture of the vulnerable plaque is the major cause of acute coronary events.

关 键 词：分子生物学 单核细胞基质金属蛋白酶的表达 逆转录聚合酶锭反应 低密度脂蛋白 氧化修饰 动脉粥样硬化 基质金属蛋白酶 免疫印迹 

分 类 号：Q786[生物学—分子生物学]