冠心舒通胶囊对ApoE^(-/-)小鼠动脉粥样硬化斑块内MMP-9和TIMP-1表达的影响

The Effect of Guanxinshutong Capsule on the Expression of Matrix Metalloproteinases-9 and Tissue Matrix Metalloproteinase Inhibitor-1 of Atherosclerotic Plaque in ApoE^(-/-) Mice

目的观察中成药冠心舒通胶囊对高脂饮食喂养ApoE-/-小鼠主动脉粥样硬化斑块病理变化、人组织型基质金属蛋白酶抑制剂1(TIMP-1)、基质金属蛋白酶9(MMP-9)表达的影响,探讨冠心舒通胶囊对粥样斑块稳定性的影响以及对相关机制进行初步研究。方法将8周龄雄性ApoE-/-小鼠30只给予高脂喂养,12周时随机分为:模型组、冠心舒通胶囊高剂量[1.8 g/(kg·天)]组和冠心舒通胶囊低剂量[0.6 g/(kg·天)]组,喂养12周后处死,取主动脉中段,大体标本油红O染色观察斑块面积,冰冻切片后HE染色观察斑块厚度,冰冻切片免疫荧光法检测斑块内TIMP-1、MMP-9表达情况。结果与模型组相比,冠心舒通胶囊组平均斑块浸润面积减小(P<0.05),弥漫程度减轻,斑块厚度降低,MMP-9表达减少,而且冠心舒通胶囊高剂量组与低剂量组相比,各项统计指标亦有统计学意义(P<0.05),TIMP-1表达未见明显变化。结论冠心舒通胶囊可以对抗ApoE-/-小鼠动脉粥样硬化斑块的形成和进展,以及通过降低斑块内MMP-9表达,从而抑制胶原纤维分解,稳定易损粥样斑块。

Aim To approach the possible mechanism of Guanxinshutong capsule on the progression and stability of atherosclerotic plaque through observing the effects of Guanxinshutong capsule on pathologic morphology and expression of tissue matrix metalloproteinase inhibitor-1（ TIMP-1）,matrix metalloproteinases-9（ MMP-9） of atherosclerotic plaque in ApoE- /-mice model with experimental atherosclerosis. Methods The animals were fed with high fat diet. They were randomly divided into 3 groups when they were 20 weeks old（ 10 mice in every group）. They were high fat diet fed group（ HF）,high fat diet and high-dose Guanxinshutong capsule [1. 8 g /（ kg·d） ]group（ HH）,high fat diet and lowdose Guanxinshutong capsule [0. 6 g /（ kg·d） ]group（ HL）. All the animals were fed for 12 weeks. After administered for 12 weeks,mice were sacrificed. The area and thickness of atherosclerotic plaque were observed by the methods of oil red O and HE stain. The expressions of TIMP-1,MMP-9 in the plaque were detected by immune fluorescence staining method. Results Compared with HF group,the changes of the area and thickness of atherosclerotic plaque in HH group and HL group were obvious（ P 0. 05）. The expression of TIMP-1 didn＇t have significant differences between groups（ P 0. 05） and MMP-9 in treatment groups were lower than those of model group（ P 0. 05）. Moreover,Significant differences were also observed between treatment groups（ P 0. 05）. Conclusion Guanxinshutong capsule can inhibit the formation and progression of atherosclerotic plaque and stabilize the unstable plaque through down-regulating the MMP-9 expression in atherosclerotic plaque,inhibiting the collagen decomposition.