The effects of oleanolic acid on atherosclerosis in different animal models
The effects of oleanolic acid on atherosclerosis in different animal models
复制标题
齐墩果酸对不同动物模型动脉粥样硬化的影响
DOI：
10.1093/abbs/gmx013
复制
发表时间：
2017-04-01
影响因子：
3.7
通讯作者：
Liu, Jun
中科院分区：
文献类型：
--
作者：
Luo, Hanqiong;Liu, Jine;Liu, Jun
本研究通过建立C57 BL/6 J小鼠、低密度脂蛋白受体（LDLR-/-）敲除小鼠和家兔动脉粥样硬化模型，探讨油酸（OA）对动脉粥样硬化的抑制作用。在家兔模型中，测定血清总胆固醇（TC）、甘油三酯（TG）、低密度脂蛋白胆固醇（LDL-C）、高密度脂蛋白胆固醇（HDL-C）。分离颈动脉病变进行组织学分析。肝组织行红油O染色和苏木精-伊红染色。测定了与脂质代谢相关的PPARγ、AdipoR 1和AdipoR 2的信使核糖核酸（mRNA）水平。与模型组比较，OA和阿托伐他汀组TC、LDL-C水平明显降低。红油O染色结果显示OA和阿托伐他汀具有相似的降脂作用。组织学结果显示OA使内膜厚度减少。与模型对照组相比，OA组AdipoR 1明显升高，AdipoR 2明显降低。在LDLR-/-小鼠模型中，测量血液中的脂质参数和PPARγ、AdipoR 1和AdipoR 2的mRNA水平。结果发现，OA表现出与阿托伐他汀相似的作用，包括降低TG、LDL-C和提高HDL-C。值得注意的是，OA升高了AdipoR 1和PPARγ的水平。OA还能降低C57 BL/6 J小鼠模型的TC和LDL-C。三种不同动物模型的实验结果均显示OA通过影响血脂水平、肝脏脂质蓄积和动脉内膜增厚延缓动脉粥样硬化的发展。OA致动脉粥样硬化的机制可能与脂质代谢相关基因：PPARγ、AdipoR 1、AdipoR 2有关。
In the present study, three animal models, including C57BL/6J mice, low-density lipoprotein receptor knockout (LDLR-/-) mice, and rabbit that mimicked atherosclerosis, were established to investigate the inhibitory effect of oleanolic acid (OA) on atherosclerosis. In rabbit model, serum total cholesterol (TC), triglyceride, low density lipoprotein cholesterol (LDL-C), and high density lipoprotein cholesterol (HDL-C) were measured. Carotid artery lesions were isolated for histological analysis. The red oil O and hematoxylin-eosin staining in liver were examined. The messenger ribonucleicacid (mRNA) levels of PPARγ, AdipoR1, and AdipoR2 related to lipid metabolism were determined. Compared with model group, OA and atorvastatin significantly lowered the levels of TC and LDL-C. The result of red oil O staining showed that OA and atorvastatin had similar effect on reducing the accumulation of lipid. Histological result demonstrated that OA reduced the thickness of intima. AdipoR1 was markedly increased, while AdipoR2 was remarkably decreased in OA group compared with that in the control group of the rabbit model. In LDLR-/- mouse model, lipid parameters in blood and mRNA levels of PPARγ, AdipoR1, and AdipoR2 were measured. It was found that OA exhibited similar effects as atorvastatin including reduced TG, LDL-C, and enhanced HDL-C. Notably, OA elevated the levels of AdipoR1 and PPARγ. At the same time, OA decreased TC and LDL-C in C57BL/6J mice model. Our results in three different animal models all revealed that OA retarded the development of atherosclerosis by influencing serum lipid levels, lipid accumulation in liver and intimal thickening of artery. And the underlying mechanism of OA on atherosclerosis may involve in lipid metabolism genes: PPARγ, AdipoR1, and AdipoR2.