Catalpol Inhibits Macrophage Polarization and Prevents Postmenopausal Atherosclerosis Through Regulating Estrogen Receptor Alpha.

Catalpol Inhibits Macrophage Polarization and Prevents Postmenopausal Atherosclerosis Through Regulating Estrogen Receptor Alpha.
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梓醇通过调节雌激素受体α抑制巨噬细胞极化并预防绝经后动脉粥样硬化

DOI:
10.3389/fphar.2021.655081
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发表时间:
2021
影响因子:
5.6
通讯作者:
Li Y
Li Y
中科院分区:
医学2区
文献类型:
--
作者:
Chen Q;Qi X;Zhang W;Zhang Y;Bi Y;Meng Q;Bian H;Li Y

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雌激素缺乏会增加绝经后女性患动脉粥样硬化(AS)的风险。炎症在AS的病理过程中起着至关重要的作用,而巨噬细胞与炎症密切相关。梓醇是从中药熟地黄新鲜根茎中提取的一种环烯醚萜苷。在本研究中,我们旨在评估梓醇对巨噬细胞极化和绝经后AS的影响。此外,我们还研究了梓醇的作用机制是否依赖于调节雌激素受体(ERs)的表达。在体外,应用脂多糖(LPS)和干扰素 - γ(IFN - γ)诱导M1巨噬细胞极化。在体内,给载脂蛋白E基因敲除(ApoE−/−)小鼠喂食高脂肪饮食以诱导AS,并进行卵巢切除术以模拟雌激素缺乏。我们发现梓醇抑制LPS和IFN - γ诱导的M1巨噬细胞极化,并减少绝经后AS小鼠的脂质堆积。梓醇不仅抑制炎症反应,还降低氧化应激水平。然后,我们还应用ERs(ERα和ERβ)抑制剂以及ERα小干扰RNA来证实梓醇的保护作用是由ERα介导的,而非ERβ。总之,梓醇通过增加ERα的表达显著抑制巨噬细胞极化并预防绝经后AS。
Lacking estrogen increases the risk of atherosclerosis (AS) in postmenopausal women. Inflammation plays a vital role in the pathological process of AS, and macrophages are closely related to inflammation. Catalpol is an iridoid glucoside extracted from the fresh roots of the traditional Chinese herb Rehmanniae radix preparata. In this study, we aimed to evaluate the effects of catalpol on macrophage polarization and postmenopausal AS. In addition, we investigated whether the mechanism of catalpol was dependent on regulating the expression of estrogen receptors (ERs). In vitro, lipopolysaccharides (LPS) and interferon-γ (IFN-γ) were applied to induce M1 macrophage polarization. In vivo, the ApoE−/− mice were fed with a high-fat diet to induce AS, and ovariectomy was operated to mimic the estrogen cessation. We demonstrated catalpol inhibited M1 macrophage polarization induced by LPS and INF-γ, and eliminated lipid accumulation in postmenopausal AS mice. Catalpol not only suppressed the inflammatory response but also reduced the level of oxidative stress. Then, ERs (ERα and ERβ) inhibitors and ERα siRNA were also applied in confirming that the protective effect of catalpol was mediated by ERα, rather than ERβ. In conclusion, catalpol significantly inhibited macrophage polarization and prevented postmenopausal AS by increasing ERα expression.
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