摘要
通过观察他汀类药物对单核细胞CD4 0和基质金属蛋白酶 9的表达是否存在抑制作用 ,初步探讨他汀类药物可能的非调脂的抗动脉粥样硬化机制。将培养的THP 1细胞中加入不同浓度的西立伐他汀 ,运用RT PCR法检测CD4 0及基质金属蛋白酶 9mRNA ,酶联免疫吸附测定法测定培养基的基质金属蛋白酶 9的浓度。结果发现 ,西立伐他汀抑制THP 1细胞CD4 0和基质金属蛋白酶 9mRNA的表达 ,并呈浓度依赖性。西立伐他汀在 0 .0 1μmol L时 ,CD4 0及基质金属蛋白酶 9的表达无明显降低 ,但在 1和 10 μmol L时 ,CD4 0mRNA的表达下调 5 5 %、89% ,基质金属蛋白酶 9mRNA的表达亦明显下降 (0 .4 5 3± 0 .13比 0 .0 73± 0 .0 1和 0 .0 0 9± 0 .0 0 1)。培养基的基质金属蛋白酶 9浓度在西立伐他汀 1和 10 μmol L时分别从 0 .4 6 9± 0 .0 6降低至 0 .2 4 3± 0 .0 4和 0 .0 39± 0 .0 1(P <0 .0 5 )。结果提示 ,西立伐他汀能抑制THP 1细胞CD4 0表达以及基质金属蛋白酶的表达和分泌 ,提示他汀类药物可减轻动脉粥样斑块炎症 ,防止斑块破裂 ,从而减少急性冠状动脉事件的发生。
Aim To investigate the effects of cerivastatin on expression of matrix metalloproteinase (MMP-9) and CD40 in THP-1 cells. Methods THP-1 cells were incubated with increasing concentration of cerivastatin. MMP-9 and CD40 mRNA were detected by RT-PCR, MMP-9 concentration in media were assayed by ELISA. Results Cerivastatin inhibited the expression of CD40 and MMP-9 concentration dependently. At 0.01 μmol/L, the mRNA levels of CD40 and MMP-9 were not significantly decreased. But expression of CD40 and MMP-9 mRNA were significant down-regulated at 1 to 10 μmol/L; Level of MMP-9 concentration in media decreased from 0.469±0.06 to 0.243±0.04 and 0.039±0.01 respectively at 1 or 10 μmol/L(P<0.05). Conclusions Cerivastatin inhibited the expression of CD40 and MMP-9 in THP-1 cells, decrease the MMP-9 concentration in media, it suggest that HMG-CoA reductase inhibitors may suppress inflammatory signaling and plaque disruption which responsible for clinical acute coronary syndrome.
出处
《中国动脉硬化杂志》
CAS
CSCD
2003年第6期533-536,共4页
Chinese Journal of Arteriosclerosis
