摘要
目的观察气血并治方提取物对ApoE基因缺陷小鼠(ApoE-小鼠)36周时动脉粥样硬化(As)的病理形态、超微结构和基质金属蛋白酶-1(MMP-1)及其抑制物-1(TIMP-1)表达的影响。方法采用6周龄ApoE-小鼠40只,给予高脂饲料。并从24周起连续给药,中药组分为大剂量组360 mg·kg-1体重(下同)和小剂量组72 mg·kg-1,阳性对照组为辛伐他汀0.52 mg·kg-1,同时取同周龄的C57BL/6小鼠做空白对照,至36周麻醉处死,利用免疫组织化学检测As斑块MMP-1和TIMP-1表达及观察As血管弹力纤维和胶原双重染色、电子显微镜下的病理变化。结果与模型组比较,气血并治方大、小剂量及辛伐他汀均能降低纤维帽厚度和脂质核心面积比值,增加斑块的纤维帽厚度等(P<0.05,P<0.01)。气血并治方大剂量组和辛伐他汀组还能减少MMP-1在As血管中的表达,增强TIMP-1的表达(P<0.05)。结论气血并治方提取物可以改善ApoE-小鼠晚期As的形成,具有保护血管内皮、抑制MMP-1的表达,改善斑块构成,稳定斑块的作用。
Abstract
OBJECTIVE To investigate the effect of water extractives of Qixue Bingzhi Fang(CWQB) on atherosclerotic labilization plaque pathology and ultrastructure(36 weeks),MMP-1 and TIMP-1 activity in apolipoprotein E-deficient mice(ApoE-mice).METHODS 40 Mice given with fat diet for 24 weeks,were randomly divided into 4 groups,which were high dose and low dose of CWQB,simvastatin and model group,10 mice in each group.The medicines were administered from 24 to 36 weeks,and the mice were sacrificed at 36 weeks.The C57BL/6 mice as control were also sacrificed.RESULTS Low and high dose of CWQB and simvastatin reduced lipid content/plaque.high dose of RQXP and simvastatin increased fibrous cap thickness and decreased plaque area/vascular size and lipid content/fiber content(P<0.05,P<0.01).High dose of WQXP and simvastatin could reduce macrophage number in plaque(P<0.05).High dose of CWQB and simvastatin increased TIMP-1 number and restrian MMP-1 activity in plaque(P<0.05).CONCLUSION CWQB could intervene labilization plaque and ultrastructure of ApoE-mice,attenuate and stabilize plaque in some extent.The mechanisms may include increasing activity of TIMP-1 adjusting MMP-1 content.
关键词
气血并治方 /
血府逐瘀汤 /
ApoE基因缺陷小鼠 /
动脉粥样硬化 /
超微结构 /
金属蛋白酶-1
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Key words
Qixue Bingzhi Fang(CWQB) /
Xufuzhuyu decoction /
apolipoprotein E-deficient mice /
atherosclerosis /
ultrastructure /
matrix metalloprotein-1
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刘剑刚;董国菊;史大卓;王永炎;程翼宇;栾连军.
气血并治方提取物对ApoE基因缺陷小鼠动脉粥样硬化病理形态和基质金属蛋白酶-1及其抑制物表达的影响[J]. 中国药学杂志, 2008, 43(22): 1700-1705
LIU Jin-gng;DONG Guo-ju;SHI D-zhuo;WNG Yong-yn;CHENG Yi-yu;LUN Lin-jun.
Effect of Water Extractives of Qixue Bingzhi Fang on Atherosclerotic Unstable Plaque Pathology and MMP-1 and TIMP-1 in Apolipoprotein E-Deficient Mice [J]. Chinese Pharmaceutical Journal, 2008, 43(22): 1700-1705
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脚注
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基金
国家重点基础研究发展规划项目课题(G1999054405)
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