Urolithin A shows anti-atherosclerotic activity via activation of class B scavenger receptor and activation of Nef2 signaling pathway
Urolithin A shows anti-atherosclerotic activity via activation of class B scavenger receptor and activation of Nef2 signaling pathway
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DOI：
10.1016/j.pharep.2017.04.020
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发表时间：
2018-06-01
影响因子：
4.4
通讯作者：
Shen, Zhen-Ya
中科院分区：
文献类型：
--
作者：
Cui, Guang-Hao;Chen, Wei-Qian;Shen, Zhen-Ya
背景资料：本研究旨在探讨尿内皮素A（urothelin A）对Wistar大鼠动脉粥样硬化（AS）的治疗作用，并探讨I型清道夫B类受体（SR-BI）和Nrf-2信号通路的激活作用。在脊髓损伤前3天，大鼠（n = 16）给予尿内皮素A（3 mg/kg/d; po）。阳性对照为接受高胆固醇饮食和主动脉球囊损伤的大鼠（n = 16）。假手术组（n = 16）：喂饲基础饲料。12周后，从所有动物收集血液用于估计脂质和血管紧张素II（Ang II）水平，随后处死所有动物并进行主动脉的形态学分析。结果：与假手术组相比，尿石素A治疗1/2周后，大鼠血脂和血管紧张素Ⅱ水平明显降低，主动脉病变明显改善。SR-BI表达增强，p-ERK 1/2表达抑制（p < 0.05）。结论：尿石素A通过上调SR-BI的表达和抑制p-ERK 1/2的表达而减轻动脉粥样硬化。(c)2017年波兰科学院药理学研究所。由爱思唯尔股份有限公司出版All rights reserved.
Background: This study investigates the therapeutic potential of urothelin A in attenuating atherosclerotic lesion in wistar rat models and explore the role of Scavenger receptor-class B type I (SR-BI) and activation of Nrf-2 singling pathway.Methods: Wistar rats (n = 48) were feed with high cholesterol diet supplemented with Vitamin D3 and subjected to balloon injury of the aorta. Three days prior to the aortal injury, rats (n = 16) were administered urothelin A (3 mg/kg/d; po). Positive control were rats receiving high cholesterol diet and balloon injury of the aorta (n = 16). The sham group (n = 16) consisted of rats fed on basal diet. After twelve weeks blood was collected from all animals for estimation of lipid and angiotensin II (Ang II) levels along, subsequently all animals were sacrificed and morphologic analysis of the aorta was performed. Expression of SR-BI and phosphorylated extracellular signal regulated kinase 1/2 (p-ERK1/2) protein were evaluated by Western blot.Results: After twelve weeks of treatment with urolithin A, there was a significant decrease in the plasma lipid and Ang II levels and improvement of aortic lesion compared with the sham group. There was an increased expression of SR-BI and inhibition of p-ERK1/2 (p < 0.05). The expression of SR-BI was inversely correlated with levels of Ang II.Conclusion: From the results it can be safely concluded that administration of urolithin A attenuates atherosclerosis via upregulation of SR-BI expression and inhibition of p-ERK1/2 levels. (c) 2017 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Sp. z o.o. All rights reserved.