摘要
As an active component extracted from Chinese herb moutan cortex and roots of paeonia lactiflora pallas, paeonol possesses many biological activities, including anti-inflammatory and vascular protection activities. In this study, athero-protective effects of paeonol were investigated in apoliprotein E deficient（Apo E^–/–） mice through the entire course of atherosclerotic development. Apo E^–/– mice were divided into five groups and fed a high-cholesterol diet（HCD） for 5, 15 and 25 weeks. Then they were fed either paeonol or atorvastatin for 6 weeks. The methods, such as ELISA for serum lipid and cytokine analyses, Western blotting for protein expressions, and HE and oil-red o-staining method, were used for evaluation of thoracic aorta lesion area. The results showed that paeonol could significantly reduce body weight, blood lipid, total cholesterol（TC）, triglyceride（TG） and low density lipoprotein（LDL-C） in Apo E^–/– mice at all stages of the atherosclerosis process. Paeonol also reduced the levels of anti-inflammation factors, such as tumor necrosis factor-α（TNF-α）, interleukin（IL）-6, oxidized LDL cholesterol（ox-LDL）, in serum. In paeonol groups, SOD was significantly increased, whereas MDA was decreased compared with the HCD group（P0.01）. Paeonol markedly attenuated the thickness of the lipid-rich plaque and down-regulated the expressions of VCAM-1 and MMP-9 in aorta of mice, suggesting that paeonol could inhibit formation of plaque and stabilize plaques. Taken together, paeonol appeared to have anti-dyslipidemia and anti-atherosclerotic effects by lipid regulation, and it could inhibit the effects of inflammation and oxidative stress on HCD-fed Apo E^–/– mice through the entire course of atherosclerotic development.
丹皮酚是从中国传统中药材牡丹皮根部所提取的活性成分,具有抗炎和保护心血管等多种生物活性。在本次实验中,丹皮酚抗动脉粥样硬化的效应贯穿于Apo E基因缺陷小鼠动脉粥样硬化疾病发展的各个时期。将Apo E基因缺陷小鼠随机分成五组,并分别给予高胆固醇(HCD)喂养5、15、25周,然后分别灌胃给丹皮酚或阿托伐他汀6周时间。采用ELISA法检测血清中脂质和细胞因子水平,蛋白质印迹法检测蛋白表达,采用H&E和油红染色法对胸主动脉病变区域进行评估。结果显示,在动脉粥样硬化疾病过程的各个阶段,丹皮酚均能显着降低ApoE^(–/–)小鼠的体重、血脂、总胆固醇(TC)、甘油三酯(TG)和低密度脂蛋白(LDL-C)水平。丹皮酚还可降低血清中的炎症因子、如肿瘤坏死因子-α(TNF-α)、白介素(IL)-6、氧化型低密度脂蛋白胆固醇(ox-LDL-C)水平。在丹皮酚组中超氧化物歧化酶(SOD)与HCD组相比显著增加而MDA(丙二醛)水平显著降低(P<0.01)丹皮酚显著减弱富含脂质斑块的厚度,下调小鼠主动脉中血管细胞粘附因子(VCAM-1)和金属基质蛋白酶(MMP-9)的表达,这表明丹皮酚可抑制斑块形成并稳定斑块。丹皮酚在Apo E基因缺陷小鼠动脉粥样硬化疾病发展的各个时期发挥了调节脂质、抗炎和抗氧化的效应,显示出其具有抗血脂异常和抗动脉粥样硬化的作用。
基金
National Natural Science Foundation of China(Grant No.81473386,81773937)
Natural Science Fund of Education Department of Anhui Province(Grant No.KJ2015A061)
Excellent Researcher Award Program of Anhui Province(Grant No.gxyq ZD2016135)
