Jia Chenglin, Xiong Minqi, Wang Peiwei, Cui Jingang, Du Xiaoye, Yang Qinbo, Wang Wenjian, Chen Yu, Zhang Teng
Yueyang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Yueyang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China; Clinical Research Institute of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
PLoS One. 2014 Jun 16;9(6):e99849. doi: 10.1371/journal.pone.0099849. eCollection 2014.
Atherosclerosis is the primary cause of cardiovascular diseases and stroke. The current study evaluated the interventional effects of a naturally occurring compound Notoginsenoside R1 (NR1) on atherosclerosis in ApoE-/- mice.
The atherosclerotic lesion was significantly alleviated by NR1 treatment and this attenuation was marked by reduction in lipid deposition, fibrosis and oxidative stress. Increased serum levels of GSH and SOD and decreased level of MDH were observed in NR1-treated ApoE-/- mice. NR1 treatment also significantly decreased the levels of CHO, TG, ox-LDL and increased the level of HDL. Additionally, the levels of inflammatory cytokines including IL-2, IL-6, TNF-α and γ-IFN were markedly reduced in NR1-treated ApoE-/- mice. Furthermore, significantly increased aortic expression of miR-26a, miR-21, miR-126a, miR-132, miR-146 and miR-155 and decreased expression of miR-20a and miR-92a were observed in the vehicle-treated ApoE-/- mice. While NR1 treatment led to a significant reduction in the expression of miR-21, miR-26a, miR-126 and increased expression of miR-20a.
Collectively, our results demonstrated for the first time the anti-atherosclerotic effects of NR1, which could be in part mediated through its multiple targeting effects on inflammation, oxidative stress, lipid metabolism and microRNA expression. These results therefore justify further evaluation of NR1 as a therapeutic agent treating atherosclerosis.
动脉粥样硬化是心血管疾病和中风的主要原因。本研究评估了天然化合物三七皂苷R1（NR1）对载脂蛋白E基因敲除（ApoE-/-）小鼠动脉粥样硬化的干预作用。
NR1治疗可显著减轻动脉粥样硬化病变，这种减轻表现为脂质沉积、纤维化和氧化应激的减少。在接受NR1治疗的ApoE-/-小鼠中，观察到血清谷胱甘肽（GSH）和超氧化物歧化酶（SOD）水平升高，丙二醛（MDH）水平降低。NR1治疗还显著降低了胆固醇（CHO）、甘油三酯（TG）、氧化低密度脂蛋白（ox-LDL）水平，提高了高密度脂蛋白（HDL）水平。此外，在接受NR1治疗的ApoE-/-小鼠中，包括白细胞介素-2（IL-2）、白细胞介素-6（IL-6）、肿瘤坏死因子-α（TNF-α）和γ-干扰素（γ-IFN）在内的炎性细胞因子水平显著降低。此外，在接受载体治疗的ApoE-/-小鼠中，观察到主动脉中微小RNA-26a（miR-26a）、微小RNA-21（miR-21）、微小RNA-126a（miR-126a）、微小RNA-132（miR-132）、微小RNA-146（miR-146）和微小RNA-155（miR-155）的表达显著增加，微小RNA-20a（miR-20a）和微小RNA-92a（miR-92a）的表达降低。而NR1治疗导致miR-21、miR-26a、miR-126的表达显著降低，miR-20a的表达增加。
总体而言，我们的结果首次证明了NR1的抗动脉粥样硬化作用，这可能部分是通过其对炎症、氧化应激、脂质代谢和微小RNA表达的多重靶向作用介导的。因此，这些结果证明有必要进一步评估NR1作为治疗动脉粥样硬化的治疗药物。
