Atherosclerosis, the leading cause of cardiovascular diseases in the world, is a chronic inflammatory disorder characterized by the dysfunction of arteries. Oleanolic acid (OA) is a bioactive nature product which exists in various plants and herbs. Previous studies have demonstrated that OA was involved in numerous of biological processes, including atherosclerosis. However, the exact mechanisms of the anti-atherosclerosis effects of OA remain unknown. Here, in our study, we analyzed the effects and possible underlying mechanisms of OA in atherosclerosis depending a cell model and an animal model of atherosclerosis. Human umbilical vein endothelial cells (HUVECs) were treated with oxidized low-density lipoprotein (ox-LDL, 100 μg/mL) for 24 h to establish an atherosclerotic cell model. New Zealand white (NZW) rabbits were fed with high-fat (HF) diets for three months to establish an atherosclerotic animal model. Then, cell viability and expression of cytokines (ANG, NO, eNOS, IL-1β, TNF-α, and IL-6) were measured with CCK-8 assay and ELISA kits, cell apoptosis and cell cycle distribution were analyzed by flow cytometry in the atherosclerotic cell model. Results showed that ox-LDL induced effects of anti-proliferation, cytokines alterations, and cell apoptosis were abolished by the application of OA or Ang (1-7). Further study indicated that OA increased the expression of ANG by upregulating the FXR expression in the ox-LDL induced HUVECs arthrosclerosis model. And the in vivo experiment in the HF diet induced animal model suggested that OA may inhibit the development of atherosclerosis. The atherosclerosis of aortas was assessed by Hematoxylin Eosin (HE), Oil Red O and Picrosirius Red staining; the expression levels of total cholesterol (TC), triglycerides (TG), low density lipoprotein cholesterol (LDL-C), and high density lipoprotein cholesterol (HDL-C) were determined by the fully automatic biochemical analyzer, in the atherosclerotic animal model. All the results showed that OA treatment improved the cell viability in the cell model, inhibited the atherosclerosis development in the animal model. OA play as an anti-atherosclerosis agent in both the cell model and animal model by upregulating the production of Angiotensin (Ang)-(1-7) through FXR.

中文翻译：

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齐墩果酸可能通过FXR介导的血管紧张素（Ang）-（1-7）上调来预防动脉粥样硬化的发病机理。

动脉粥样硬化是世界上心血管疾病的主要原因，是一种以血管功能障碍为特征的慢性炎症性疾病。齐墩果酸（OA）是一种生物活性的天然产物，存在于多种植物和草药中。先前的研究表明，OA与许多生物过程有关，包括动脉粥样硬化。然而，OA的抗动脉粥样硬化作用的确切机制仍然未知。在这里，在我们的研究中，我们根据动脉粥样硬化的细胞模型和动物模型分析了OA在动脉粥样硬化中的作用及其可能的潜在机制。用氧化的低密度脂蛋白（ox-LDL，100μg/ mL）处理人脐静脉内皮细胞（HUVEC）24小时，以建立动脉粥样硬化细胞模型。新西兰白（NZW）兔饲喂高脂（HF）饲料三个月，以建立动脉粥样硬化动物模型。然后，使用CCK-8分析和ELISA试剂盒检测细胞活力和细胞因子（ANG，NO，eNOS，IL-1β，TNF-α和IL-6）的表达，并通过流式细胞仪分析细胞凋亡和细胞周期分布在动脉粥样硬化细胞模型中 结果表明，通过使用OA或Ang（1-7）可以消除ox-LDL诱导的抗增殖，细胞因子改变和细胞凋亡的作用。进一步的研究表明，在ox-LDL诱导的HUVEC动脉硬化模型中，OA通过上调FXR表达来增加ANG的表达。HF饮食诱导的动物模型的体内实验表明，OA可能抑制动脉粥样硬化的发展。用苏木精曙红（HE），油红O和皮克罗西里乌斯红染色评估主动脉的动脉粥样硬化。在动脉粥样硬化动物模型中，通过全自动生化分析仪测定总胆固醇（TC），甘油三酸酯（TG），低密度脂蛋白胆固醇（LDL-C）和高密度脂蛋白胆固醇（HDL-C）的表达水平。所有结果表明，OA处理改善了细胞模型中的细胞活力，抑制了动物模型中动脉粥样硬化的发展。OA通过上调FXR上调血管紧张素（Ang）-（1-7）的产生，在细胞模型和动物模型中均充当抗动脉粥样硬化剂。动脉粥样硬化动物模型中的全自动生化分析仪测定了高密度脂蛋白胆固醇和高密度脂蛋白胆固醇（HDL-C）。所有结果表明，OA处理改善了细胞模型中的细胞活力，抑制了动物模型中动脉粥样硬化的发展。OA通过上调FXR上调血管紧张素（Ang）-（1-7）的产生，在细胞模型和动物模型中均充当抗动脉粥样硬化剂。动脉粥样硬化动物模型中的全自动生化分析仪测定了高密度脂蛋白胆固醇和高密度脂蛋白胆固醇（HDL-C）。所有结果表明，OA处理改善了细胞模型中的细胞活力，抑制了动物模型中动脉粥样硬化的发展。OA通过上调FXR上调血管紧张素（Ang）-（1-7）的产生，在细胞模型和动物模型中均充当抗动脉粥样硬化剂。