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目的观察三七、绞股蓝及其总皂苷对动脉粥样硬化模型家兔主动脉基质金属蛋白酶及其抑制因子表达的影响,并从基因水平探讨其作用机制。方法40只新西兰兔随机分为5组,即三七绞股蓝饮片组、三七绞股蓝总皂苷组、阳性药物组、模型组与正常对照组,以高脂饲料和免疫损伤联合复制动脉粥样硬化模型,各药物组在造模的同时预防给药,12周后检测各组实验兔血清脂质水平,观察兔主动脉病理学变化,RT-PCR检测主动脉壁基质金属蛋白酶9(MMP-9)、基质金属蛋白酶抑制剂1(TIMP-1)表达水平。结果模型组的血清总胆固醇(TC)、三酰甘油(TG)、低密度脂蛋白胆固醇(LDL-C)的含量均明显高于正常对照组(P<0.01),三七绞股蓝饮片组的TC明显低于模型组(P<0.05),三七绞股蓝总皂苷组的TG明显低于模型组(P<0.05)。各药物预防组的主动脉病理形态学变化与模型组比较有明显差异(P<0.01,P<0.05)。与正常对照组比较,模型组的主动脉组织MMP-9mRNA的表达明显增强,TIMP-1mRNA的表达明显减弱。与模型组比较,三七绞股蓝饮片组、皂苷组的MMP-9mRNA表达量水平均降低,TIMP-1mRNA的表达明显增加。结论三七绞股蓝配伍可调节MMP-9/TIMP-1mRNA的表达,降低血脂水平,具有抗动脉粥样硬化作用,下调主动脉组织MMP-9mRNA的表达,上调TIMP-1mRNA的表达可能是其作用机制之一。
Objective To observe the effects of Panax notoginseng and gypenosides on the expression of matrix metalloproteinase and its inhibitor in the aorta of rabbits with atherosclerosis and to explore its mechanism from the gene level. Methods Forty New Zealand white rabbits were randomly divided into five groups: the Sanqi Gynostemma Pentaphylla, Sanqi Gypenosides, the positive drug group, the model group and the normal control group. The model of atherosclerosis was duplicated with high fat diet and immune injury , And each drug group was given prophylactic administration at the same time of modeling. After 12 weeks, serum lipid levels of experimental rabbits in each group were measured and the pathological changes of aorta were observed. The expression of matrix metalloproteinase 9 (MMP-9) , Matrix metalloproteinase inhibitor 1 (TIMP-1) expression levels. Results The levels of total cholesterol (TC), triglyceride (TG) and low density lipoprotein cholesterol (LDL-C) in the model group were significantly higher than those in the normal control group (P <0.01) (P <0.05). The TG of gynostemma saponins group was significantly lower than that of model group (P <0.05). The pathological changes of the aorta in each drug prevention group were significantly different from the model group (P <0.01, P <0.05). Compared with the normal control group, the expression of MMP-9mRNA in aortic tissue of the model group was significantly increased, and the expression of TIMP-1mRNA was significantly decreased. Compared with the model group, the MMP-9 mRNA expression level of Sanqi Gynostemma pentaphylla group and saponin group decreased, and the expression of TIMP-1mRNA increased significantly. Conclusions Panzhi Gynostemma pentaphyllum can regulate the expression of MMP-9 / TIMP-1mRNA, decrease the level of blood lipid, anti-atherosclerosis, down-regulate the expression of MMP-9mRNA in aorta and up-regulate the expression of TIMP-1mRNA one.