人参皂苷衍生物CK201抗动脉粥样硬化活性及其机制的实验研究

冉晓冬; 罗明明; 王嘉维; 黄琰; 李晓辉

doi:10.16016/j.2097-0927.202301066

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人参皂苷衍生物CK201抗动脉粥样硬化活性及其机制的实验研究

基础医学 | 更新时间：2026-01-09

- 人参皂苷衍生物CK201抗动脉粥样硬化活性及其机制的实验研究
- Anti-atherosclerotic activity and mechanism of a ginsenoside derivative CK201
- 陆军军医大学学报 2023年45卷第10期页码：1010-1019
- 作者机构：
  
  1.400038 重庆，陆军军医大学(第三军医大学)药学与检验医学系药物研究所
  2.400054 重庆，重庆理工大学药学与生物工程学院
- 作者简介：
  
  [李晓辉，E-mail: lpsh008@aliyun.comLI Xiaohui, E-mail: lpsh008@aliyun.com
- 基金信息：
  
  国家自然科学基金面上项目(81773742)
- DOI：10.16016/j.2097-0927.202301066
  中图分类号： R282.71;R285.5;R543.5
- 收稿：2023-01-12，
  
  修回：2023-03-08，
  
  纸质出版：2023-05-30
- 稿件说明：
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冉晓冬, 罗明明, 王嘉维, 等. 人参皂苷衍生物CK201抗动脉粥样硬化活性及其机制的实验研究[J]. 陆军军医大学学报, 2023,45(10):1010-1019.

Xiaodong RAN, Mingming LUO, Jiawei WANG, et al. Anti-atherosclerotic activity and mechanism of a ginsenoside derivative CK201[J]. Journal of Army Medical University, 2023, 45(10): 1010-1019.
冉晓冬, 罗明明, 王嘉维, 等. 人参皂苷衍生物CK201抗动脉粥样硬化活性及其机制的实验研究[J]. 陆军军医大学学报, 2023,45(10):1010-1019. DOI： 10.16016/j.2097-0927.202301066.

Xiaodong RAN, Mingming LUO, Jiawei WANG, et al. Anti-atherosclerotic activity and mechanism of a ginsenoside derivative CK201[J]. Journal of Army Medical University, 2023, 45(10): 1010-1019. DOI： 10.16016/j.2097-0927.202301066.

摘要

目的

使用ApoE

-/-

小鼠和人脐静脉内皮细胞(human umbilical vein endothelial cells

HUVECs)研究人参皂苷衍生物CK201抗动脉粥样硬化(atherosclerosis

AS)活性及其初步机制。

方法

体内实验：30只6周龄雄性ApoE

-/-

小鼠通过完全随机分组法分为5组：溶剂对照组、模型组、compound K(CK)组、阿托伐他汀钙组及CK201组。除溶剂对照组，其余每组给予高脂饲料喂养，同时CK组、阿托伐他汀钙组和CK201组分别灌胃3 mg/kg对应化合物。主动脉油红O染色评估CK201及阿托伐他汀钙对动脉粥样硬化斑块形成的影响；检测血浆TC、TG水平，考察CK201及阿托伐他汀钙对小鼠血脂的影响；Western blot分析CK201及阿托伐他汀钙对主动脉IL-6、TNF-α表达水平的影响；肝组织切片HE和油红O染色评估CK201及阿托伐他汀钙对肝脏脂质堆积的影响；检测小鼠肝、肾功能和血常规以初步评估CK201对相关指标的影响。体外实验：Western blot分析CK201对棕榈酸(palmitic acid

PA)刺激HUVECs细胞产生IL-6、TNF-α水平的影响；HUVECs细胞划痕愈合实验、单核细胞(THP-1)与HUVECs细胞黏附实验分析CK201对HUVECs细胞迁移、募集单核细胞能力的影响。

结果

CK201比同剂量的阳性对照药阿托伐他汀钙(斑块抑制率62.4%

26.6%)更显著地抑制高脂喂养的ApoE

-/-

小鼠主动脉粥样硬化斑块的形成(

＜0.05)；CK201可以显著减少肝脏脂质沉积，明显优于阿托伐他汀钙(

＜0.05)。CK201能显著降低血浆中TC含量、抑制主动脉炎症因子IL-6和TNF-α的表达(

＜0.05)，抑制PA刺激的HUVECs细胞炎症因子IL-6和TNF-α的表达、减少THP-1细胞对HUVECs细胞的黏附、促进HUVECs细胞迁移(

＜0.05)。肝功能和血常规检测表明，实验剂量的CK201对小鼠肝功能和血常规均无明显影响。

结论

人参皂苷衍生物CK201具有显著的抗AS作用，其机制可能与其降低血浆TC水平、抑制主动脉炎症反应、抑制单核细胞与内皮细胞的黏附等有关。

Abstract

Objective

To explore the anti-atherogenic activity and mechanism involved of ginsenoside derivative CK201 by ApoE

-/-

mouse and human umbilical vein endothelial cells (HUVECs).

Methods

In vivo

experiment: 6-week-old male ApoE

-/-

mice(

=30) were randomly divided into 5 groups: the solvent control group

the model group

the ginsenoside compound K(CK) group

the atorvastatin calcium group and the CK201 group. Except the solvent control group

mice in other groups were fed high-fat diet. At the same time

mice in the CK group

the atorvastatin calcium group and the CK201 group were administrated intragastrically 3 mg/kg compound

respectively. The effect of CK201 and atorvastatin calcium on the formation of AS plaque was evaluated by aorta oil red O staining. The plasma levels of TC and TG were detected

and the effects of CK201 and atorvastatin calcium on blood lipid in mice were investigated. Western blot assay was used to analyze the effects of CK201 and atorvastatin calcium on the expression of inflammatory factors IL-6 and TNF-α of the aorta. The effects of CK201 and atorvastatin calcium on liver lipid accumulation were evaluated by HE and oil red O staining in liver sections. Liver and kidney function tests and blood routine tests of mice were performed to evaluate the effect of CK201 on related indicators.

In vitro

experiments: Western blot assay was used to analyze the effects of CK201 on the levels of IL-6 and TNF-α in HUVE

Cs cells stimulated by palmitic acid. The effects of CK201 on the migration and recruitment of monocytes of HUVECs were analyzed by the scratch healing experiment of HUVECs cells and the adhesion experiment between monocytes (THP-1) and HUVECs cells.

Results

The CK201 group significantly inhibited the formation of atherosclerotic aortic plaques in ApoE

-/-

mice fed with high-fat diet

compared with the atorvastatin calcium group (plaque inhibition rate: 62.4%

26.6%

0.05). The CK201 group had significantly reduced hepatic lipid accumulation

which had significantly better effect than those in the atorvastatin calcium group(

0.05). In the CK201 group

TC content in plasma was significantly decreased

the expressions of IL-6 and TNF-α in aorta were inhibited(

0.05)

the expression of palmitic acid-stimulated inflammatory cytokines IL-6 and TNF-α in HUVECs cells was inhibited

the adhesion of THP-1 cells to HUVECs cells was reduced

and the migration of HUVECs cells was promoted(

0.05). In addition

the experimental dose of CK201 had no significant effect on the liver function and blood routine tests.

Conclusion

CK201

a ginsenoside derivative

has a significant anti-atherosclerosis effect

and the mechanism involved may be related to the reduction of plasma TC level

inhibition of aortic inflammation

inhibition of cell adhesion of monocyte and endothelial cells.

关键词

Keywords

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