Digoxin reduces atherosclerosis in apolipoprotein E-deficient mice
Digoxin reduces atherosclerosis in apolipoprotein E-deficient mice
复制标题
地高辛可减少载脂蛋白 E 缺陷小鼠的动脉粥样硬化
DOI：
10.1111/bph.13453
复制
发表时间：
2016-05-01
影响因子：
7.3
通讯作者：
Zeng, Qiutang
中科院分区：
文献类型：
--
作者：
Shi, Huairui;Mao, Xiaobo;Zeng, Qiutang
背景和目的大量体外研究表明地高辛可抑制炎症并改变脂质代谢。然而，二恶英对动脉粥样硬化的影响知之甚少。实验方法给维持西式饮食的载脂蛋白E缺陷小鼠施用PBS（对照），小剂量地高辛（1 mg kg（-1）天（-1））或高剂量地高辛（2 mgkg（-1）day（-1））腹腔注射12周。关键结果地高辛剂量依赖性地减少动脉粥样硬化病变的形成和血脂水平（高剂量地高辛治疗组中总胆固醇降低41%，甘油三酯降低54%，低密度脂蛋白胆固醇降低20%）。此外，地高辛治疗显着衰减IL-17 A的表达和IL-17 A相关的炎症反应，并增加了丰富的调节性T细胞（T细胞）。结论和影响我们的数据表明，地高辛作为一种特异性拮抗剂维甲酸相关的孤儿受体-通过抑制血脂水平和IL-17 A相关的炎症反应，以减少动脉粥样硬化。
Background and PurposeNumerous in vitro studies have suggested that digoxin suppresses inflammation and alters lipid metabolism. However, the effect of dioxin on atherosclerosis is poorly understood. The present study was conducted to determine whether digoxin affects the development of atherosclerosis in a murine model of atherosclerotic disease.Experimental ApproachApolipoprotein E-deficient mice maintained on a Western-type diet were administered PBS (control), low-dose digoxin (1mgkg(-1) day(-1)) or high-dose digoxin (2mgkg(-1) day(-1)) via i.p. injection for 12weeks.Key ResultsDigoxin dose-dependently reduced atherosclerotic lesion formation and plasma lipid levels (reductions of 41% in total cholesterol, 54% in triglycerides and 20% in low-density lipoprotein cholesterol in the high-dose digoxin-treated group). Moreover, treatment with digoxin markedly attenuated IL-17A expression and IL-17A-related inflammatory responses and increased the abundance of regulatory T cells (Tregs).Conclusions and ImplicationsOur data demonstrate that digoxin acts as a specific antagonist of retinoid-related orphan receptor- to decrease atherosclerosis by suppressing lipid levels and IL-17A-related inflammatory responses.