洛伐他汀对血管平滑肌细胞基质金属蛋白酶3表达的影响  

Effect of Lovastatin on Secretion of Matrix Metalloproteinase-3 in Vascular Smooth Muscle Cells

作　　者：栾朝霞[1] 高沁怡[2] 裴著果[3] 

机构地区：[1]中国医科大学第三临床学院,辽宁省沈阳市110022 [2]中国医科大学第一临床学院,辽宁省沈阳市110022 [3]中国医科大学第二临床学院,辽宁省沈阳市110022

出　　处：《中国动脉硬化杂志》2003年第4期339-341,共3页Chinese Journal of Arteriosclerosis

摘　　要：观察洛伐他汀对兔血管平滑肌细胞基质金属蛋白酶 3表达的影响及其作用机制。用Westernblot检测基质金属蛋白酶 3蛋白水平 ,采用电泳迁移率变动分析法测定AP 1结合活性 ,用逆转录聚合酶链反应检测基质金属蛋白酶 3mRNA水平。结果发现 ,白细胞介素 1α和血小板源生长因子BB联合作用于兔血管平滑肌细胞 ,可明显增加基质金属蛋白酶 3的表达 ,洛伐他汀抑制这种刺激作用 ,使基质金属蛋白酶 3的表达减低 ,且呈浓度依赖性 ;该抑制作用可被甲羟戊酸和双香叶酯基焦磷酸盐所逆转 ,而不被角鲨烯所逆转。白细胞介素 1α和血小板源生长因子BB联合作用后使兔血管平滑肌细胞AP 1结合活性和基质金属蛋白酶 3mRNA水平明显增高 ,洛伐他汀抑制白细胞介素 1α和血小板源生长因子BB上调AP 1结合活性的作用 ,但对基质金属蛋白酶 3mRNA水平无明显影响。结果提示 ,洛伐他汀不依赖其调脂作用抑制血管平滑肌细胞基质金属蛋白酶 3的生成 。Aim To investigate the effect of lovastatin on secretion of matrix metalloproteinase 3 (MMP 3) in cultured vascular smooth muscle cells (VSMC) of rabbits. Methods Expression of MMP 3 was detected by Western blot, AP 1 binding activity was detected by electrophoretic mobility shift assay (EMSA), mRNA level of MMP 3 was detected by reverse transcription polymerase chain reaction (RT PCR). Results Interleukin 1α (IL 1α) combined with platelet derived growth factor BB (PDGF BB) strongly increased the expression of MMP 3 at VSMC. Lovastatin inhibited the upregulated expression of MMP 3 by IL 1α and PDGF BB in a concentration dependent manner. This inhibitory effect was reversed by mevalonate and GGPP, but not by squalene. Lovastatin decreased AP 1 binding activity enhanced by IL 1α and PDGF BB, but had no significant effect on MMP 3 mRNA level. Conclusion Lovastatin inhibited MMP 3 secretion at VSMC, which could contribute to its plaque stablising effects.

关 键 词：内科学 洛伐他汀抑制基质金属蛋白酶3的表达 WestemBlot检测法 血管平滑肌细胞 白细胞介素1Α 血小板源生长因子BB 动脉粥样硬化 

分 类 号：R5[医药卫生—内科学]