赤芍川芎有效部位对兔动脉粥样硬化基质金属蛋白酶的影响

作者	单位
张璐	中国中医科学院西苑医院心血管中心
薛梅	中国中医科学院西苑医院心血管中心
马晓娟	中国中医科学院西苑医院心血管中心
杨琳	中国中医科学院西苑医院心血管中心
殷惠军	中国中医科学院西苑医院心血管中心

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中文摘要:

目的观察芎芍胶囊(XSC,赤芍川芎有效部位)对兔动脉粥样硬化模型中基质金属蛋白酶(matrix metalloproteinases,MMPs)表达水平的影响。方法50只新西兰兔随机分为正常对照组、模型对照组、辛伐他汀组、XSC低剂量组和XSC高剂量组,每组10只。正常对照组普通饲料喂养,其余各组高脂饲料喂养,2周后行腹主动脉球囊导管血管损伤术,建立动脉粥样硬化模型,继续高脂喂养,辛伐他汀组给予辛伐他汀2.5mg/(kg·d),XSC低、高剂量组分别给予芎芍胶囊0.24g/(kg·d)和0.48g/(kg·d),连续给药6周后,各组采血测血脂;酶联免疫法测定血清MMP-3、MMP-9和MMP组织抑制因子-1(TIMP-1)的表达;免疫组化方法检测斑块组织MMP-3及白细胞分化抗原40配体(CD40L)的蛋白表达。结果与模型对照组比较,辛伐他汀组、XSC高、低剂量组血清MMP-3、MMP-9水平显著下降(P<0.05),同时斑块内MMP-3和CD40L表达也明显降低(P<0.05,P<0.01);辛伐他汀组和XSC高、低剂量组较模型对照组对血清总胆固醇均有不同程度的下降(P<0.05,P<0.01),辛伐他汀组还显著降低血清甘油三酯和低密度脂蛋白胆固醇;各组TIMP-1变化差异无统计学意义(P>0.05)。结论赤芍川芎有效部位具有一定稳定斑块的作用,抑制动脉粥样硬化模型兔血管壁中和血清MMP-3、MMP-9及相关因子表达,可能是其可能机制之一。

英文摘要:

Objective To investigate the effect of the active components from Red Paeonia and Rhizoma chuanxiong (in Xiongshao Capsule,XSC) on matrix metalloproteinases (MMPs) in rabbit model of atherosclerosis. Methods Fifty New Zealand rabbits were randomly divided into the normal control group (A),the model control group (B),the Simvastatin treated group (C),the low-dose XSC treated group (D) and the high-dose XSC treated group (E),10 in each group. Rabbits in the normal control group were fed with normal diet,while those in the other four groups were fed with high fat diet and duplicated after two weeks feeding into model of abdominal aortic atherosclerosis by balloon angioplasty. In the 6 successive weeks feeding of high fat diet,Simvastatin 2.5 mg/kg,XSC 0.24 g/kg and 0.48 g/kg per day was given respectively to the rabbits in the three treated groups. Blood sample was collected for determining the level of blood lipids;serum MMP-3 and MMP-9,and tissue inhibitor of metalloproteinase-1 (TIMP-1) with enzyme-linked immunoassay;and the protein expression of MMP-3 and cluster of differentiation antigen 40 ligand (CD40L) in plaque were detected with immunohistochemical method. Results Compared with Group B,the serum levels of MMP-3 and MMP-9;the expression of MMP-3 and CD40L in plaque;and the blood content of total cholesterol in the three treated groups were significantly lower (P<0.05 or P<0.01). Besides,the content of triglyceride and low-density lipoprotein cholesterol were significantly reduced in Group C,while the TIMP-1 showed no statistical difference among different groups (P>0.05). Conclusion The active components of Red Paeonia and Rhizoma chuanxiong play a definite role in stabilizing the atherosclerotic plaque in rabbits,one of their possible mechanisms may be by way of inhibiting the expressions of MMP-3,MMP-9 in vascular walls and blood serum.

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