摘要目的 探讨黄芪水提取物对载脂蛋白E基因敲除( ApoE-/-)小鼠主动脉粥样硬化斑块部位基质金属蛋白酶-9(MMP-9)表达及斑块形成的影响.方法 将48只8周龄雄性ApoE -/-小鼠给予高脂饮食喂养,小鼠20周龄时根据随机表按照完全随机法分为4组各12只,即对照组、阿托伐他汀组、黄芪水提取物低剂量组及黄芪水提取物高剂量组.对照组给予生理盐水0.2 ml/d,阿托伐他汀组给予阿托伐他汀10 mg·kg-1·d-1,黄芪水提取物低剂量给予黄芪水提取物1.25 g·kg-1·d-1、黄芪水提取物高剂量给予黄芪水提取物5 g·kg-1·d-1灌胃.予给药12周末处死各组小鼠.应用ELISA法测定血清氧化低密度脂蛋白(oxLDL)含量；HE染色、油红O染色观察小鼠主动脉粥样斑块内脂质的形成；用免疫荧光、免疫组化染色法检测观察粥样斑块部位巨噬细胞浸润水平及MMP-9表达.结果 黄芪水提取物明显降低ApoE.小鼠,其中黄芪水提取物高剂量组血清oxLDL含量明显低于对照组[(5.2±6.1) μg/ml比(15.8±5.4) μg/ml,P＜0.01]；与对照组比较,黄芪水提取物高剂量组ApoE-/--小鼠动脉粥样斑块面积明显减小(17.24％±4.22％比49.87％±9.37％,P＜0.01),动脉管壁斑块弥漫程度较轻(P＜0.01).黄芪水提取物高剂量组斑块中Mac3表达低于对照组(P＜0.01)；黄芪水提取物高剂量组与对照组主动脉斑块中MMP-9阳性表达面积平均吸光度值(MA)分别为0.0154±0.0014与0.0263±0.0065 (P ＜0.01).结论 黄芪水提取物能够抑制ApoE-/-小鼠动脉MMP-9表达,延缓动脉粥样硬化斑块形成.其机制可能是通过降低ApoE-/-小鼠血清oxLDL水平,抑制巨噬细胞的浸润、迁移及分泌MMP-9,从而抑制斑块形成.

abstractsObjective To explore the effects of astragali radix extract on the expressions of matrix metalloproteinase 9(MMP-9) and the formation of atherosclerotic plaque in aortic atherosclerotic plaques of apolipoprotein E-deficient mice (ApoE -/- ).Methods Male 8-week-old ApoE-/- mice fed with high fat diet were randomly divided into four groups ( n =12 each):control group ( saline 0.2 ml/d),atorvastatin group (atorvastatin 10 mg · kg-1 · d-1),low-dose astragali radix extract group (1.25 g · kg-1 · d-1) and high-dose astragali radix extract group(5 g · kg-1 · d-1 ).After 12 weeks,serum oxLDL was measured by the method of ELISA.The formation of atherosclerotic plaque was determined in HE and oil red O stained aortic slice.The expressions of macrophage and MMP-9 in the aortic plaque were detected by immune fluorescence and immunohistochemistry staining method.Results Similarly as atorvastatin,astragali radix extract significantly decreased the level of serum oxLDL in ApoE / - mice in a dose-dependent manner.The level of oxLDL in the high-dose astragali radix extract group [ ( 5.2 ± 6.1 ) μg/ml ] was significantly lower than that in the control group[ ( 15.8 ±5.4) μg/ml,P ＜0.01 ].The area of atherosclerosis plaques was smaller ( 17.24％ t 4.22％ vs.49.87％ ± 9.37％,P ＜ 0.01 ) and the penetration degree of plaques in the arterial wall was relieved in the high-dose astragali radix extract group compared to those in the control group (P ＜0.01 ).The expressions of Mac3 in atherosclerosis plaques of the high-dose astragali radix extract group was also significantly lower than in the control group (P＜0.01 ).The mean absorbance value of the expression of MMP-9 in the high-dose astragali radix extract group (0.0154 ± 0.0014)was significantly lower than that in the control group (0.0263 ± 0.0065 ) ( P ＜ 0.01 ).Conclusions Similar as atorvastatin,astragali radix extract can dose-dependently inhibit the expression of MMP-9 and the formation of the atherosclerotic plaque in ApoE-/- mouse,probably by reducing the serum oxLDL,inhibiting macrophage infiltration,migration and secretion of MMP-9.