丹皮酚减缓动脉粥样硬化病变的形成及发展涉及脂质调节, 抗炎和抗氧化活性

doi:10.5246/jcps.2018.08.057

中国药学(英文版) ›› 2018, Vol. 27 ›› Issue (8): 565-575.DOI: 10.5246/jcps.2018.08.057

丹皮酚减缓动脉粥样硬化病变的形成及发展涉及脂质调节, 抗炎和抗氧化活性

宋爱伟^1,2, 吴鸿飞^1,3, 戴敏^1,2*

1. 安徽中医药大学药学院, 安徽合肥 230031
2. 安徽省中药研究与开发重点实验室, 安徽合肥 230031
3. 新安医学教育部重点实验室, 安徽合肥 230031

收稿日期:2018-04-30 修回日期:2018-06-13 出版日期:2018-09-04 发布日期:2018-06-25
通讯作者: Tel.: +86-0551-65619221, E-mail: daiminliao@163.com
基金资助:
National Natural Science Foundation of China (Grant No. 81473386, 81773937), Natural Science Fund of Education Department of Anhui Province (Grant No. KJ2015A061) and Excellent Researcher Award Program of Anhui Province (Grant No. gxyqZD2016135).

Paeonol attenuates progression of atherosclerotic lesion formation through lipid regulation, anti-inflammatory and antioxidant activities

Aiwei Song^1,2, Hongfei Wu^1,3, Min Dai^1,2*

1. Department of Pharmacy, Anhui University of Traditional Chinese Medicine, Hefei 230031, China
2. Key Laboratory of Chinese Medicine Research and Development, Hefei 230031, China
3. Key Laboratory of Xin'an Medicine, Hefei 230031, China

Received:2018-04-30 Revised:2018-06-13 Online:2018-09-04 Published:2018-06-25
Contact: Tel.: +86-0551-65619221, E-mail: daiminliao@163.com
Supported by:
National Natural Science Foundation of China (Grant No. 81473386, 81773937), Natural Science Fund of Education Department of Anhui Province (Grant No. KJ2015A061) and Excellent Researcher Award Program of Anhui Province (Grant No. gxyqZD2016135).

摘要/Abstract

摘要：

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ApoE基因缺陷小鼠动脉粥样硬化疾病发展的各个时期。将ApoE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ApoE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。

关键词: 丹皮酚, ApoE基因缺陷小鼠, 动脉粥样硬化, 脂质调节, 抗炎, 抗氧化活性

Abstract:

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-protectiveeffects of paeonol were investigated in apoliprotein E deficient (ApoE^–/–) mice through the entire course of atherosclerotic development. ApoE^–/–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 H&E 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 ApoE^–/–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 (P<0.01). 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 ApoE^–/–mice through the entire course of atherosclerotic development.

Key words: Paeonol, ApoE-deficient mice, Atherosclerosis, Lipids regulation, Anti-inflammatory, Antioxidant activities

中图分类号:

R962

Supporting:

宋爱伟, 吴鸿飞, 戴敏. 丹皮酚减缓动脉粥样硬化病变的形成及发展涉及脂质调节, 抗炎和抗氧化活性[J]. 中国药学(英文版), 2018, 27(8): 565-575.

Aiwei Song, Hongfei Wu, Min Dai . Paeonol attenuates progression of atherosclerotic lesion formation through lipid regulation, anti-inflammatory and antioxidant activities[J]. Journal of Chinese Pharmaceutical Sciences, 2018, 27(8): 565-575.

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丹皮酚减缓动脉粥样硬化病变的形成及发展涉及脂质调节, 抗炎和抗氧化活性

Paeonol attenuates progression of atherosclerotic lesion formation through lipid regulation, anti-inflammatory and antioxidant activities

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