细胞色素P450基因降低动脉粥样硬化小鼠MMP-9表达  

Arachidonic Acid Cytochrome P450 Epoxygenase Reduces Expression of MMP-9 on Atherosclerosis Mice Model

作　　者：吴俊[1] 陈琛[1] 曾和松[1] 汪道文[1] 

机构地区：[1]湖北武汉华中科技大学同济医学院附属同济医院心血管内科,武汉430030

出　　处：《中国分子心脏病学杂志》2010年第6期344-347,共4页Molecular Cardiology of China

基　　金：科技部973计划课题(编号2006CB503801)

摘　　要：目的研究血管内皮高表达CYP2C8基因能否降低动脉粥样硬化小鼠的MMP-9的表达。方法以20周龄APOEKO+/-CYP2C8Tg+/-和CYP2C8Tg+/-小鼠(n=10/组)为研究对象,相同基因背景和周龄的同窝APOEKO+/-和C57BL/6小鼠设为对照。采用PCR技术鉴定小鼠CYP2C8+/-基因;油红O染色检测APOEKO+/-CYP2C8Tg+/-、CYP2C8Tg+/-、APOEKO+/-和C57BL/6小鼠主动脉斑块形成面积;用Real-time PCR法检测各组小鼠的主动脉MMP-9基因表达水平,Western blot分析各组小鼠的主动脉MMP-9蛋白的表达情况。用ELISA法检测各组小鼠的血浆IL-1β和IL-10。结果 APOEKO+/-CYP2C8Tg+/-和CYP2C8Tg+/-小鼠主动脉斑块形成面积明显减少,Real-time PCR分析显示高表达CYP2C8在主动脉中明显下调MMP-9基因的表达,Western blot分析结果显示:高表达CYP2C8在主动脉中明显下调MMP-9蛋白的活性。在血清学上,高表达CYP2C8明显上调IL-10而下调IL-1β。结论高表达CYP2C8基因能够降低小鼠的MMP-9的活性、减低炎性介质水平,通过抗炎和稳定粥样斑块而发挥抗粥样硬化作用。Objective To study whether overexpression of arachidonic acid cytochrome P450 epoxygenase gene 2C8(CYP2J8)reduce the expression of MMP-9 in atherosclerosis mice.Methods 20-week-old APOEKO+/-Tie-CYP2C8Tg+/-and Tie-CYP2C8Tg+/-mice were exposed to high-fat food for 20 weeks to induce atherosclerosis.When the mice were sacrificed at 20 week,the index of atherosclerotic formation was measured by oil red O and Aorta MMP-9 was measured by Quantitative real-time PCR.Expression of MMP-9 in aorta were explored by western blot and plasma IL-1β and IL-10 were measured by ELISA.Results Overexpression of CYP2C8 genes can ameliorate atherosclerotic formation in aortic.Quantitative real-time PCR showed the expression of MMP-9 genes in aortic were reduced by overexpression of CYP2C8.Western blot showed that the expression of MMP-9 protein in aortic were reduced by overexpression of CYP2C8.Overexpression of CYP2C8 significantly elevated plasma levels of IL-10,anti-inflammatory factor,in contrast decreased plasma levels of IL-1β.Conclusion There findings suggest that overexpression of CYP2C8 gene can reduce the expression of MMP-9 on atherosclerosis mice.

关 键 词：细胞色素P450 环氧化二十碳三烯酸 动脉粥样硬化 MMP-9 

分 类 号：R543[医药卫生—心血管疾病]