二甲双胍通过基质金属蛋白酶抑制血管内皮损伤后的内膜增生  

Metformin Prevents Intimal Hyperplasia After Arterial Injury via Inhibiting Matrix Metalloproteinases

作　　者：王强[1] 杨大春[1] 马双陶[1] 张彦[1] 李德[1] 唐兵[1] 杨永健[1] 

机构地区：[1]成都军区总医院心血管内科,四川省成都市610083

出　　处：《中国动脉硬化杂志》2014年第11期1087-1090,共4页Chinese Journal of Arteriosclerosis

基　　金：国家自然科学基金项目(81100232);全军医学科技青年培育项目(13QNP058)

摘　　要：目的观察二甲双胍对血管内皮损伤后内膜增生的影响,并探讨其可能机制。方法选用300~350 g的健康雄性SD大鼠45只,随机分为对照组、颈动脉球囊损伤组、颈动脉球囊损伤＋二甲双胍组,3周后HE染色观察内膜增生情况,real-time PCR、Western blot和免疫组织化学染色检测颈动脉组织中基质金属蛋白酶2（MMP-2）、基质金属蛋白酶9（MMP-9）的表达情况。结果球囊损伤后,颈动脉出现明显的内膜增生,颈动脉组织中MMP-2、MMP-9的mRNA和蛋白表达显著上调（P〈0.01）;二甲双胍削弱血管内皮损伤所致MMP-2和MMP-9的表达上调（P〈0.05）,并抑制血管内皮损伤后的内膜增生（P〈0.01）。结论二甲双胍可能通过抑制MMP-2和MMP-9的表达防止血管损伤后内膜增生。Aim To investigate the effect of metformin on intimal hyperplasia after arterial injury and explore the underlying mechanisms. Methods Male SD rats were randomly divided into control group,carotid arterial balloon injury group and carotid arterial balloon injury plus metformin group,15 rats in each group. After the intervention for three weeks,the histological structure of carotid artery was evaluated by HE staining,the expressions of matrix metalloproteinase（ MMP）-2 and MMP-9 were determined by real-time PCR,Western blot and immunohistochemistry staining. Results Intimal hyperplasia was caused by carotid arterial balloon injury. The expressions of MMP-2 and MMP-9 in carotid artery were significantly upregulated after balloon injury（ P 〈 0. 01）. Treatment of metformin attenuated the upregulation of MMP-2 and MMP-9 and inhibited intimal hyperplasia induced by arterial injury（ P 〈 0. 05 or P 〈 0. 01）. Conclusions Metformin may prevent intimal hyperplasia through inhibiting MMP-2 and MMP-9 expression after arterial injury.

关 键 词：血管内皮损伤 内膜增生 二甲双胍 基质金属蛋白酶 

分 类 号：R96[医药卫生—药理学]