阿托伐他汀对鼠动脉粥样硬化基质金属蛋白酶2、9的影响

Effect of atorvastatin on the expression of matrix metalloproteinase-2,9 in aorta of atherosclerotic rats

目的 :研究阿托伐他汀对动脉粥样硬化鼠主动脉基质金属蛋白酶 2、9表达的影响。方法 :将清洁级雌性SD大鼠 5 0只分为正常对照组 (n =10 ,正常饮食 )、基础对照组 (n =2 0 ,维生素D3(VD3) +高脂饲料 )、阿托伐他汀治疗组 (n =2 0 ,VD3+高脂饲料和阿托伐他汀 )。 4个月后处死 ,取主动脉起始部做病理切片 ,进行光镜观察 ;剩余的主动脉抽提总蛋白 ,用免疫印迹法检测基质金属蛋白酶 2、9蛋白质的表达。结果 :阿托伐他汀能显著降低鼠血浆总胆固醇、甘油三酯、低密度脂蛋白 ,抑制动脉粥样硬化的形成 ;同时显著降低动脉粥样硬化鼠主动脉基质金属蛋白酶 2、9的表达 ,正常对照组、基础对照组、阿托伐他汀治疗组主动脉中表达的基质金属蛋白酶 2相对值分别为 (5 314± 16 3)、(86 18± 5 4 9)、(3397± 4 5 3) ,相互间有显著的统计学差异 (P<0 .0 1)。基质金属蛋白酶 9在各组主动脉中表达的相对值分别为 (6 178± 2 5 4 )、(90 5 4± 35 0 )、(6 80 5± 36 8) ,相互间有显著的统计学差异 (P <0 .0 1)。结论 :阿托伐他汀可以显著降低动脉粥样硬化血管组织基质金属蛋白酶的表达 ,抑制动脉粥样硬化的形成。

Objective:To investig ate the effect of atorvastatin on the expression of matrix metalloproteinase-2 ,9 in aorta of atherosclerotic rats . Methods:Sprague-Dawley(SD) rats were studied ,the rats were fe d with a normal diet( n=10) or a cholesterol diet(1% cholesterol;0.5% sodium ch olat e;0.1% methimazole;5%lard,n=40) for 8 weeks; cholesterol fed rats underwent intr aperitoneal vitamin D3 injection (700,000IU/kg,usually four times at th e inter val of two days) before initiation of the diet, a half of whom were fed with ato rvast atin (5mg·kg -1·d -1) after two months. After another two months, all the aorta were harvested for west blot studies. Results:Atorvastatin could remarkably lower plasma total choles terol,low density lipoprotein, triglyceride and inhibit the formation of athero sc lerosis. Matrix metalloproteinase-2 of west blot results were as follows: (5314 ±163),(8618±549),(3397±453),respectively,with significant difference among them(P<0.01);and matrix metalloproteinase-9: (6178±254),( 905 4±350),( 6805±368),respectively,with significant difference among them( P<0.01). Conclusion:Atorvastatin can decrease the expression of matrix m etalloproteinases, which benefit the reversion of atherosclerosis.