何首乌总苷抗氧化与实验性小鼠主动脉粥样硬化病变的形成

Effect of PMTG on atherosclerotic lesion formation and expression of ICAM-1 and VCAM-1 in ApoE-deficient mice

目的:研究何首乌总苷(polygonum multiflorum total glycoside,PMTG)的抗氧化性及对载脂蛋白E基因缺陷(apoprotein E gene deficiency,ApoE-/-)小鼠实验性动脉粥样硬化(atherosclerosis,As)病变形成的影响。方法:将ApoE-/-小鼠随机分为4组:何首乌总苷高剂量组(150 mg.kg-1.d-1)、低剂量组(25 mg.kg-1.d-1)、阿托伐他汀阳性药物组(5 mg.kg-1.d-1)及模型组,给药第10周后全部处死,酶法检测4组血清脂质含量;化学法测氧化指标一氧化氮(NO)、总抗氧化能力(TAC)及丙二醛(MDA);电镜观察主动脉壁内皮细胞形态变化以及免疫组织化学染色方法测定ApoE-/-小鼠主动脉壁NFκB的表达。结果:实验10周后,何首乌总苷高、低剂量组及阳性药物组与模型组比较,显示:①可以显著降低血清总胆固醇(TC),甘油三酯(TG)及低密度脂蛋白-胆固醇(LDL-C)水平(P<0.01);②明显增加血浆NO及TAC(P<0.05及P<0.01),减少MDA的生成(P<0.01);③电镜观察发现何首乌总苷可以维持主动脉壁内皮细胞正常形态;④抑制ApoE-/-小鼠主动脉壁核因子-κB(NF-κB)的表达(P<0.01)。结论:何首乌总苷可能通过抗氧化保护主动脉内皮细胞形态,降低ApoE-/-小鼠氧化型LDL(ox-LDL)、减少主动脉壁NF-κB的表达,从而下调主动脉壁ICAM-1及VCAM-1的表达等环节延缓主动脉斑块的形成,起到防止ApoE-/-小鼠实验性动脉粥样硬化病变形成的作用。

Objective： To study the protecting effect of polygoni multiflori total glycosides （PMTG） on the atherosclerotic lesion formation and the expression of ICAM-1, VCAM-1 in aolipoprotein （apo） E-deficient transgenic mice. Method： Thirty-two female apoE-deficienct mice were randomized into four groups： PMTG high dose group （150 mg·kg·d）, low dose group （25 mg·kg·d）, atorvastatin positive control group （5 mg·kg·d）, and model group. At the end of the tenth week, all mice were killed. The serum levels of Total cholesterol （TC）, Triglyceride （TG）, High-density lipoprotein-cholesterol （LDL-C） were measured by enzyme dynamics method. Transmission electron microscopy （TEM） were used to observe the morphologic changes of aortic endothelia cell. The expressions of NF-κB were studied by SABC immunohistochemistry. Result： As compared with the model control group. （1）PMTG could reduce the levels of serum TC, TG significantly （P 〈0. 01）, and LDL-C level significantly （P 〈0. 01）. （2）It could increase the levels of serum NO and the anti-oxidation capacities significantly （P 〈 0. 01 ）, but reduce the levels of serum MDA significantly （P 〈 0. 01）. （3）PMTG could keep the normal morphology of aortic endothelial cell. （4）PMTG could deregulated the expression of NF-κB in aortic wall. Conclusion： PMTG could inhibit the occurrence and development of atherosclerotic lesions by its anti-oxidation abilities, which reduce LDL-C level. The low LDL-C level could deregulated the of expression of NF-κB, which could deregulated ICAM-1 and VCAM-1 in AopE-/-mice in aortic wall through.