何首乌总苷对ApoE-/-小鼠动脉粥样硬化病变形成的影响

目的:研究何首乌总苷(polygonum multiflorum total glycoside,PMTG)对载脂蛋白E基因缺陷(ApoE-/-)小鼠实验性动脉粥样硬化(atherosclerosis,AS)病变形成及细胞间黏附分子-1(intercellular adhesion molecule-1,ICAM-1)与血管细胞黏附分子-1(vascular cell adhesion molecule-1,VCAM-1)的表达影响,探讨何首乌总苷抑制AS病变形成的可能机制。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)及模型对照组。给药第10周后全部处死,检测4组血清脂质含量,一氧化氮(NO),总抗氧化能力(TAOC),丙二醛(MDA),主动脉AS粥样斑块面积及其与管腔面积的比值,主动脉壁ICAM-1及VCAM-1表达。结果:何首乌总苷高、低剂量组及阳性药物组与模型对照组ApoE-/-小鼠比较,显示:①何首乌总苷高、低剂量可以显著降低血清总胆固醇(TC),甘油三酯(TG)水平(P<0.01),升高高密度脂蛋白(HDL)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何首乌总苷可减轻AS病变,减小斑块面积与管腔面积比值(P<0.05);④何首乌总苷可下调ICAM-1及VCAM-1的表达(P<0.01)。结论:何首乌总苷可能通过调节ApoE-/-小鼠血脂代谢、增强其抗氧化能力及下调主动脉壁ICAM-1及VCAM-1表达等上述环节的共同作用与影响,阻止ApoE-/-小鼠实验性动脉粥样硬化病变形成的发生、发展。

The effects of polygoni multiflori total glycosides on the experimentally atherosclerotic formation in ApoE-deficient mice

Objective: To study the effect of polygoni multiflori total glycosides(PMTG) on the expressions of ICAM-1 and VCAM-1 in the apoE-deficienct(ApoE-/-)mice with experimental atherosclerosis(AS) and underlying mechanism.Method: Thirty-two female apoE-deficienct mice were randomized into four groups: high dose PMTG group(150 mg·kg^-1·d^-1),low dose PMTG group(25 mg·kg^-1·d^-1),atorvastatin positive control group(5 mg·kg^-1·d^-1) and model group.At the end of the tenth week of treatment,all mice were killed.The serum levels of total cholesterol(TC),triglyceride(TG),high-density lipoprotein-cholesterol(HDLC) were measured by enzyme dynamics method.Light microscopy were adopted to assess the degree of atherosclerotic plaque of aortic wall and image analysis was performed with computer.The expressions of ICAM-1 and VCAM-1 were studied by SABC imunohistochemistry.Result: In comparison with the model group,(1)PMTG reduced the levels of serum TC and TG significantly(P<0.01),but elevated HDL level obviously(P<0.01).(2)PMTG increased the levels of serum NO and the anti-oxidation capacities significantly(P<0.05 and P<0.01),but reduced the levels of serum MDA markedly((P<0.01)).(3)PMTG reduced also the extent of atherosclerotic plaque of aorta areas were(P<0.05).(4)PMTG deregulated the expressions of ICAM-1 and VCAM-1 in aortic wall.Conclusion: PMTG could inhibit the occurrence and development of atherosclerotic lesions by the regulating lipid metabolism and anti-oxidation and deregulating the of expressiona of ICAM-1 and VCAM-1 in AopE-/-mice in aortic wall.