Molecular mechanism of astragaloside Ⅳ against atherosclerosis by regulating miR-17-5p and PCSK9/VLDLR signal pathway.
10.19540/j.cnki.cjcmm.20210918.701
- Author:
He-Wei QIN
1
;
Qin-Sheng ZHANG
2
;
Yan-Jie LI
2
;
Wen-Tao LI
3
;
Yuan WANG
3
Author Information
1. Second Affiliated Hospital of Henan University of Traditional Chinese Medicine Zhengzhou 450002, China Henan University of Chinese Medicine Zhengzhou 450002, China.
2. Second Affiliated Hospital of Henan University of Traditional Chinese Medicine Zhengzhou 450002, China.
3. Henan University of Chinese Medicine Zhengzhou 450002, China.
- Publication Type:Journal Article
- Keywords:
astragaloside Ⅳ;
atherosclerosis;
microribonucleic acid 17-5p;
vascular endothelial cells
- MeSH:
Animals;
Atherosclerosis/genetics*;
Lipoproteins, LDL/metabolism*;
Mice;
MicroRNAs/metabolism*;
Proprotein Convertase 9/metabolism*;
Receptors, LDL/metabolism*;
Saponins;
Signal Transduction;
Triterpenes
- From:
China Journal of Chinese Materia Medica
2022;47(2):492-498
- CountryChina
- Language:Chinese
-
Abstract:
This study explores the regulatory effect of astragaloside Ⅳ on miR-17-5 p and its downstream proprotein convertase subtillisin/kexin type 9(PCSK9)/very low density lipoprotein receptor(VLDLR) signal pathway, aiming at elucidating the mechanism of astragaloside Ⅳ against atherosclerosis(AS). In cell experiment, oxidized low-density lipoprotein(ox-LDL) was used for endothelial cell injury modeling with vascular smooth muscle cells(VSMCs). Then cells were classified into the model group, miR-17-5 p inhibitor group, blank serum group, and astragaloside Ⅳ-containing serum group based on the invention. Afterward, cell viability and the expression of miR-17-5 p, VLDLR, and PCSK9 mRNA and protein in cells in each group were detected. In animal experiment, 15 C57 BL/6 mice were used as the control group, and 45 ApoE~(-/-) mice were classified into the model group, miR-17-5 p inhibitor group, and astragaloside Ⅳ group, with 15 mice in each group. After 8 weeks of intervention, the peripheral serum levels of interleukin-6(IL-6), interleukin-10(IL-10), and tumor necrosis factor-α(TNF-α), and the expression of miR-17-5 p, VLDLR, and PCSK9 mRNA in the aorta of mice were detected. The pathological changes of mice in each group were observed. According to the cell experiment, VSMC viability in the miR-17-5 p inhibitor group and the astragaloside Ⅳ-containing serum group was higher than that in the model group(P<0.05). The mRNA and protein expression of miR-17-5 p and VLDLR in VSMCs in the miR-17-5 p inhibitor group and the astragaloside Ⅳ-containing serum group was lower than that in the model group(P<0.05), but the mRNA and protein expression of PCSK9 was higher than that in the model group(P<0.05). As for the animal experiment, the levels of IL-6 and TNF-α in the peripheral serum of the miR-17-5 p inhibitor group and the astragaloside Ⅳ group were lower(P<0.05) and the serum level of IL-10 was higher(P<0.05) than that of the model group. The mRNA expression of miR-17-5 p and VLDLR in the aorta in the miR-17-5 p inhibitor group and the astragaloside Ⅳ group was lower(P<0.05), and PCSK9 mRNA expression was higher(P<0.05) than that in the model group. Pathological observation showed mild AS in the miR-17-5 p inhibitor group and the astragaloside Ⅳ group. In summary, astragaloside Ⅳ can prevent the occurrence and development of AS. The mechanism is that it performs targeted regulation of miR-17-5 p, further affecting the PCSK9/VLDLR signal pathway, inhibiting vascular inflammation, and thus alleviating endothelial cell injury.
