Jiang Weiwei, Cen Yanyan, Song Yi, Li Pan, Qin Rongxin, Liu Chao, Zhao Yibo, Zheng Jiang, Zhou Hong
Department of Pharmacology, College of Medicine, The Third Military Medical University, Chongqing 400038, P. R. China.
Medical Research Center, Southwestern Hospital, The Third Military Medical University, Chongqing 400038, P. R. China.
Phytomedicine. 2016 Oct 15;23(11):1259-66. doi: 10.1016/j.phymed.2016.06.004. Epub 2016 Jun 6.
Inflammation plays an important role in all stages of atherosclerosis, but little is known about the therapeutic effects of quenching inflammation in atherosclerotic lesions formation.
Herein, the effect of artesunate, a derivant from artemisinin from the traditional Chinese herb sweet wormwood, could attenuate the progression of atherosclerosis lesion formation alone or combined with rosuvastatin in Western-type diet (WD) fed ApoE(-/-) mice, and explored its possible mechanisms.
The methods such as ELISA for plasma lipids and cytokines analyses, qRT-PCR and western blot for mRNA and protein expressions, and MTT assay for human umbilical vein endothelial cells (HUVECs) viability were used for in vivo and in vitro experiments.
Artesunate could attenuate the progression of atherosclerosis lesion formation alone or combined with rosuvastatin in WD fed ApoE(-/-) mice without changes in food uptake, body weight and plasma lipids level, but with a significant reduction of pro-inflammatory cytokine, such as TNF-α and IL-6. Furthermore, artesunate could down-regulate the pro-inflammatory chemokines such as IL-8 and MCP-1 in aorta of mice. Besides, artesunate didn't influence IL-8 and MCP-1 secretion in HUVECs up-regulated by TNF-α, but inhibited IL-8 and MCP-1 secretion up-regulated by LPS.
AS attenuated progression of atherosclerosis lesion formation alone or combined with rosuvastatin through anti-inflammatory effect, resulting in down-regulation of TNF-α and IL-6, and further down-regulating IL-8 and MCP-1 expressions in aorta of WD fed ApoE(-/-) mice. Rosuvastatin combined with artesunate could more effectively attenuate the progression of atherosclerosis lesions than when treated by one of them, demonstrating that lipid-lowering agents combined with anti-inflammatory agents could provide the greater benefit for cardiovascular disease patients. Artesunate is worth further investigating as a candidate drug for the treatment of atherosclerosis.
炎症在动脉粥样硬化的各个阶段都起着重要作用，但关于抑制炎症对动脉粥样硬化病变形成的治疗效果知之甚少。
本文研究青蒿素（一种源自传统中药青蒿的衍生物）单独或与瑞舒伐他汀联合使用时，对喂食西方型饮食（WD）的载脂蛋白E基因敲除（ApoE(-/-)）小鼠动脉粥样硬化病变形成进展的影响，并探讨其可能的机制。
采用酶联免疫吸附测定法（ELISA）分析血浆脂质和细胞因子、实时定量聚合酶链反应（qRT-PCR）和蛋白质免疫印迹法检测mRNA和蛋白质表达，以及噻唑蓝比色法（MTT法）检测人脐静脉内皮细胞（HUVECs）活力等方法进行体内和体外实验。
青蒿素单独或与瑞舒伐他汀联合使用时，均可减轻喂食WD的ApoE(-/-)小鼠动脉粥样硬化病变的进展，且不影响食物摄取、体重和血浆脂质水平，但可显著降低促炎细胞因子，如肿瘤坏死因子-α（TNF-α）和白细胞介素-6（IL-6）。此外，青蒿素可下调小鼠主动脉中促炎趋化因子，如白细胞介素-8（IL-8）和单核细胞趋化蛋白-1（MCP-1）。此外，青蒿素不影响肿瘤坏死因子-α上调的人脐静脉内皮细胞中白细胞介素-8和单核细胞趋化蛋白-1的分泌，但可抑制脂多糖上调的白细胞介素-8和单核细胞趋化蛋白-1的分泌。
青蒿素单独或与瑞舒伐他汀联合使用，通过抗炎作用减轻动脉粥样硬化病变的进展，导致肿瘤坏死因子-α和白细胞介素-6下调，并进一步下调喂食WD的ApoE(-/-)小鼠主动脉中白细胞介素-8和单核细胞趋化蛋白-1的表达。瑞舒伐他汀与青蒿素联合使用比单独使用其中一种药物能更有效地减轻动脉粥样硬化病变的进展，表明降脂药物与抗炎药物联合使用可为心血管疾病患者带来更大益处。青蒿素作为治疗动脉粥样硬化的候选药物值得进一步研究。
