Apple Polyphenols Decrease Atherosclerosis and Hepatic Steatosis in ApoE-/- Mice through the ROS/MAPK/NF-κB Pathway.
Apple Polyphenols Decrease Atherosclerosis and Hepatic Steatosis in ApoE-/- Mice through the ROS/MAPK/NF-κB Pathway.
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DOI：
10.3390/nu7085324
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发表时间：
2015-08-24
期刊：
影响因子：
5.9
通讯作者：
Yang YM
中科院分区：
文献类型：
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作者：
Xu ZR;Li JY;Dong XW;Tan ZJ;Wu WZ;Xie QM;Yang YM
在这项研究中，我们研究了苹果多酚（APs）对高脂血症，动脉粥样硬化，肝脂肪变性和内皮功能的影响，并探讨了潜在的机制。ApoE−/−小鼠喂食西式饮食，并口服AP（100 mg/kg）或阿托伐他汀（10 mg/kg）12周。测量了主动脉窦和肝动脉的高血压和动脉粥样硬化。AP或阿托伐他汀治疗可显著减少动脉粥样硬化病变和肝脂肪变性，并降低血浆中低密度脂蛋白、甘油三酯、CCL-2和VCAM-1水平。相反，AP显着增加血浆高密度脂蛋白（HDL）胆固醇水平，并显着上调谷胱甘肽过氧化物酶（GPx），过氧化氢酶（CAT）和超氧化物歧化酶（SOD）水平在肝组织中。此外，AP处理通过上调包括PPARα在内的相关肝脏基因的转录，同时下调与肝脏脂质合成相关的SCAP及其下游基因的转录来调节脂质代谢。组织学评估显示AP处理还减少了主动脉根部斑块中的巨噬细胞浸润和炎性细胞向肝组织的浸润。此外，我们证实，AP治疗大大降低了氧化低密度脂蛋白诱导的内皮功能障碍和单核细胞粘附大鼠主动脉内皮细胞（RAECs）。APs处理抑制ROS/MAPK/NF-κB信号通路，从而降低CCL-2、ICAM-1和VCAM-1的表达。我们的研究结果表明，AP是一种有益的营养补充剂，用于衰减动脉粥样硬化。
In this study, we examined the effects of apple polyphenols (APs) on hyperlipidemia, atherosclerosis, hepatic steatosis and endothelial function and investigated the potential mechanisms. ApoE−/− mice were fed a western-type diet and orally treated with APs (100 mg/kg) or atorvastatin (10 mg/kg) for 12 weeks. Hyperlipidemia and atherosclerosis in the aortic sinuses and, and hepatic lipidosis were measured. The treatment with APs or atorvastatin induced a remarkable reduction in the atherosclerotic lesions and hepatic steatosis and decreased the levels of low-density lipoprotein, triglyceride, CCL-2 and VCAM-1 levels in the plasma. Conversely, the APs significantly increased the plasma levels of high-density lipoprotein (HDL) cholesterol and markedly up-regulated the glutathione peroxidase (GPx), catalase (CAT) and superoxide dismutase (SOD) levels in liver tissues. Moreover, the APs treatment modulated lipid metabolism by up-regulating the transcription of associated hepatic genes including PPARα, while down-regulating the transcription of SCAP and its downstream genes associated with lipid synthesis in the liver. Histological assessment showed that the APs treatment also reduced the macrophage infiltration in the aortic root plaque and the inflammatory cells infiltrations to the liver tissues. Moreover, we confirmed that the APs treatment greatly reduced the ox-LDL-induced endothelial dysfunction and monocyte adhesion to rat aortic endothelial cells (RAECs). Mechanistically, the APs treatment suppressed the ROS/MAPK/NF-κB signaling pathway, and consequently, reduced CCL-2, ICAM-1 and VCAM-1 expression. Our results suggest that the APs are a beneficial nutritional supplement for the attenuation of atherosclerosis.