Berberine activates peroxisome proliferator-activated receptor gamma to increase atherosclerotic plaque stability in Apoe(-/-) mice with hyperhomocysteinemia.

Berberine activates peroxisome proliferator-activated receptor gamma to increase atherosclerotic plaque stability in Apoe(-/-) mice with hyperhomocysteinemia.
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小檗碱激活过氧化物酶体增殖物激活受体γ以增加高同型半胱氨酸血症Apoe(-/-)小鼠的动脉粥样硬化斑块稳定性

DOI:
10.1111/jdi.12516
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发表时间:
2016-11
影响因子:
3.2
通讯作者:
Liu N
Liu N
中科院分区:
医学3区
文献类型:
--
作者:
Li H;He C;Wang J;Li X;Yang Z;Sun X;Fang L;Liu N

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血浆同型半胱氨酸水平升高一直被怀疑是糖尿病患者发生动脉粥样硬化性血管疾病的代谢危险因素。小檗碱(BBR)对心血管疾病具有多种预防作用。BBR对同型半胱氨酸硫代内酯(HTL)增加的动脉粥样硬化斑块稳定性的影响尚不清楚。通过在Apoe −/−小鼠的颈动脉周围放置项圈来诱导动脉粥样硬化易损斑块模型。通过器官室测定内皮依赖性舒张。同型半胱氨酸硫代内酯(50 mg/kg/天,8周)降低了Apoe −/−小鼠颈动脉中的动脉粥样硬化斑块稳定性,BBR给药(1.0 g/kg/天)可逆转该作用。体内和离体实验表明,HTL显着降低乙酰胆碱诱导的内皮依赖性舒张和超氧化物歧化酶活性,并增加丙二醛含量,这是由BBR抑制。重要的是,BBR诱导的所有效应均被GW 9662(过氧化物酶体增殖物激活受体-γ的拮抗剂)消除。培养的内皮细胞与HTL孵育显着降低细胞活力和活性氧的产生增加。用BBR剂量依赖性地预处理细胞逆转了HTL诱导的有害作用,这是GW 9662可逆的。小檗碱增加高同型半胱氨酸血症小鼠动脉粥样硬化斑块的稳定性,这与过氧化物酶体增殖物激活受体γ的激活和随后抑制内皮细胞中的氧化应激有关。血浆同型半胱氨酸水平升高一直被怀疑是糖尿病患者发生动脉粥样硬化性血管疾病的代谢危险因素。我们报道了小檗碱作为一种天然产物,增加高同型半胱氨酸血症小鼠动脉粥样硬化斑块的稳定性,这与激活过氧化物酶体增殖物激活受体γ和随后抑制内皮细胞的氧化应激有关。
An elevated level of plasma homocysteine has long been suspected as a metabolic risk factor for the development of atherosclerotic vascular diseases in diabetes. Berberine (BBR) has several preventive effects on cardiovascular diseases. The effects of BBR on atherosclerotic plaque stability increased by homocysteine thiolactone (HTL) remain unknown. The model of atherosclerotic vulnerable plaque was induced by placing a collar around the carotid artery in Apoe −/− mice. Endothelium‐dependent relaxation was assayed by organ chamber. Homocysteine thiolactone (50 mg/kg/day, 8 weeks) reduced the atherosclerotic plaque stability in the carotid artery of Apoe −/− mice, which was reversed by BBR administration (1.0 g/kg/day). In vivo and ex vivo experiments showed that HTL dramatically reduced acetylcholine‐induced endothelium‐dependent relaxation and superoxide dismutase activity, and increased malondialdehyde content, which were inhibited by BBR. Importantly, all effects induced by BBR were abolished by GW9662, an antagonist of peroxisome proliferator‐activated receptor‐γ. Incubation of cultured endothelial cells with HTL significantly reduced cell viabilities and enhanced production of reactive oxygen species. Pretreatment of cells with BBR dose‐dependently reversed HTL‐induced detrimental effects, which were GW9662‐reversible. Berberine increases atherosclerotic plaque stability in hyperhomocysteinemia mice, which is related to the activation of peroxisome proliferator‐activated receptor‐γ and subsequent suppression of oxidative stress in endothelial cells. An elevated level of plasma homocysteine has long been suspected as a metabolic risk factor for the development of atherosclerotic vascular diseases in diabetes. We reported that berberine, as a natural production, increase atherosclerotic plaque stability in hyperhomocysteinaemia mice, which is related to the activation of PPARγ and subsequent suppression of oxidative stress in endothelial cells.
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