首参颗粒对动脉粥样硬化大鼠血清MMP-9、TIMP-1表达的影响

Impacts of Shoushen Keli on the Expressions of Serum MMP-9 and TIMP-1 in the Rats with Atherosclerosis

目的观察首参颗粒对动脉粥样硬化(AS)大鼠血清基质金属蛋白酶-9(MMP-9)及基质金属蛋白酶组织抑制剂-1(TIMP-1)的干预作用。方法 40只雄性SD大鼠,随机分为正常组、模型组、西药对照组(西药组)、首参颗粒组(中药组),每组10只。除正常组外,其余大鼠均以高脂饲料喂养,并一次性腹腔注射维生素D3,以建立AS模型。同时模型组灌服生理盐水,中药组灌服首参颗粒,西药组灌服普伐他汀进行药物干预。12周后HE染色观察各组大鼠血管病理变化,ELISA法检测大鼠血清MMP-9及TIMP-1含量。结果模型组大鼠病理切片可见部分动脉内膜断裂,内皮细胞排列明显紊乱。中药组动脉内膜较模型组光滑平整,内膜脱落、内皮细胞排列紊乱较模型组明显减轻。模型组大鼠血清MMP-9含量较正常组明显增高(P<0.01),而TIMP-1含量明显降低(P<0.01)。与模型组相比较,中药组MMP-9含量明显降低(P<0.01),TIMP-1含量明显增高(P<0.05)。结论首参颗粒可能通过抑制MMP-9、促进TIMP-1的表达,调节MMP-9/TIMP-1的失衡状态,改善动脉粥样硬化病变。

Objective To observe the intervention effect of shoushen keli on serum matrix metalloproteinases-9 （MMP-9） and tissue inhibitor of metalloproteinases-1 （TIMP-1） in the rats with arteriosclerosis （AS）.Methods Forty male SD rats were randomized into a normal group,a model group,a western medicine control group（western medicine group）and a shoushen keli group（Chinese medicine group）,10 rats in each one.Except in the normal group,the high fat diet was used in the rest groups and intraperitoneal injection of vitamin D was applied to set up AS model.At the same time,the physiological saline was infused in the model group,shoushen keli was in the Chinese medicine group and pravastatin was in the western medicine group for medicinal intervention.In 12 weeks,HE staining was used to observe the pathological changes in rat vessels of each group.ELISA was adopted to determine the levels of serum MMP-9 and TIMP-1.Resuits The pathological section displayed partial rupture of endarterium,obvious disarrangement of endothelial cells in the model group.Endarterium was smoother,and intimal detachment and disarrangement of endothelial cells were alleviated apparently in the Chinese medicine group as compared with the model group.MMP-9 level in the model group was obviously higher than that in the normal group（P ＜ 0.01）and TIMP-1 level was apparently reduced（P ＜0.01）.Compared with the model group,MMP-9 level was reduced apparently（P ＜ 0.01） and TIMP-1 level was increased apparently（P ＜ 0.05） in the Chinese medicine group.Conclusion Shoushen keli relieves AS possibly through inhibiting MMP-9 expression,promoting TIMP-1 expression and regulating the imbalance of MMP-9/TIMP-1.