正脂方对动脉粥样硬化兔MMP-9及TIMP-1水平的影响  

The effects of Zhengzhifang on reversing atherosclerosis by regulating MMP-9 and TIMP-1

作　　者：黄曾艳 黄曼萍[2] 梁东辉[1] 刘永源[2] 江伟强[2] 张薇[2] 

机构地区：[1]南方医科大学中医药学院,广州510515 [2]南方医科大学珠江医院中医科,广州510280

出　　处：《广东医学》2016年第15期2224-2227,共4页Guangdong Medical Journal

基　　金：国家自然科学基金资助项目(编号:81072935);广东省自然科学基金资助项目(编号:S2013010015883)

摘　　要：目的观察正脂方对动脉粥样硬化(AS)兔基质金属蛋白酶-9(MMP-9)及基质金属蛋白酶组织抑制物-1(TIMP-1)表达的影响及可能的作用机制。方法 31只新西兰兔随机分成4组:空白组(5只)、模型组(8只)、正脂方组(10只)、氟伐他汀组(8只),除空白组外采用喂饲高脂饲料法建立高脂血症模型,分别予生理盐水、生理盐水、正脂方3 g/(kg·d)及氯伐他汀灌胃。分别在实验开始当天及实验第12、16周后采集耳缘静脉血检测血脂[包括总胆固醇(TC)、三酰甘油(TG)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)];第16周动物处死后取主动脉根部行常规石蜡切片及油红O染色,观察AS病变程度及分析动脉脂质沉积情况,并采用免疫组化法检测AS斑块中MMP-9和TIMP-1的光密度值。结果与空白组比较,模型组TC、LDL-C水平明显升高(P<0.05);空白组未见AS病变,而模型组可见动脉粥样硬化斑块形成,脂质沉积严重;与模型组比较,正脂方组及氟伐他汀组皆可降低主动脉硬化程度、减轻血管壁的脂质沉积,并可降低血清TC、LDL-C水平(P<0.05);模型组可见HDL-C水平升高(P<0.05),MMP-9的表达水平下调(P<0.05),TIMP-1的表达升高。结论正脂方有明显降低TC及LDL-C、升高HDL-C的作用,同时有逆转动脉壁脂质沉积的作用,其抗AS的功效可能与其抑制AS模型兔血管壁中MMP-9及提高TIMP-1的表达有关。Objective To investigate the effects of Zhengzhifang on matrix metalloproteinase（ MMP- 9） and tissue inhibitor of metalloproteinase- 1（ TIMP- 1） in rabbits with atherosclerosis（ AS） and its possible mechanism. Methods High fat diet was applied to establish the hyperlipidaemia（ HLP） model. New Zealand rabbits were randomly divided into 4 groups： normal group（ n = 5）,model group（ n = 8）,Zhengzhifang group（ n = 10）,and fluvastatin group（ n =8）. Blood lipids（ including TG,TC,LDL- C and HDL- C） were collected at baseline,12 thand 16thweek. MMP- 9and TIMP- 1 were assessed with immunohistochemistry. Results Compared with model group,the severity of AS was significantly alleviated in Zhengzhifang group,with significantly lower serum total cholesterol and low- density lipoprotein levels（ P〈0. 05）. So was significant increase of high- density lipoprotein,down- regulation of MMP- 9 and up- regulation of TIMP- 1（ P〈0. 05）. Conclusion Zhengzhifang can significantly lower serum LDL- C and CHOL,and increase HDL- C. This effect may be related to the inhibition of MMP- 9 and enhance of TIMP- 1 in vascular wall in AS rabbits.

关 键 词：正脂方 动脉粥样硬化 基质金属蛋白酶 

分 类 号：R575.2[医药卫生—消化系统]