三七、绞股蓝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

Effects of Panax notoginseng and Gynostemma pentaphyllum on matrix metalloproteinase and its tissue inhibitor in abdominal aorta of rabbits

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 effect of Panax notoginseng and Gynostemma pentaphyllum on matrix metalloproteinase and the tissue inhibitor of metalloproteinase mRNA expression in abdominal aorta of experimental atherosclerosis rabbits and to explore its mechanisms.Methods Thirty-two male New Zealand rabbits were fed with high-fat diet（HFD） and randomly divided into Panax notoginseng and Gynostemma pentaphyllum group（PNG）,Panax notoginseng saponins and gypenosides group（PNSG）,Captopril group（CAP）,and placebo group;eight normal diet rabbits were served as normal control group.Serum lipid levels were measured 12 weeks later,as well as pathomorphological change of abdominal aorta.MMP-9 and TIMP-1 mRNA expressions were demonstrated by reverse transcription polymerase chain reaction（RT-PCR）.Results Total cholesterol（TC）,total triglyceride（TG） and low-density lipoprotein-cholesterol（LDL-c） levels were significantly higher in HFD rabbits than normal diet rabbits（P〈0.01）.TC level was lower in PNG group than placebo group,TG level was lower in PNSG group than placebo group（P〈0.05）.Pathomorphological index in PNG,PNSG and CAP groups were lower than placebo group（P〈0.01）.MMP-9 mRNA expression was up-regulated in placebo group in comparison with normal diet group,while TIMP-1 mRNA expression was down-regulated in placebo group（P〈0.05）.MMP-9 mRNA expression was lower in both PNG and PNSG groups than placebo group,while TIMP-1 mRNA expression was higher in both PNG and PNSG group than placebo group（P〈0.05）.Conclusion Panax notoginseng and Gynostemma pentaphyllum can attenuate serum lipid level and mitigate aorta pathomorphology by down-regulating MMP-9 mRNA expression and upvregulating TIMP-1 mRNA expression.