Article: [Molecular mechanism of astragaloside Ⅳ against atherosclerosis by regulating miR-17-5p and PCSK9/VLDLR signal pathway].
Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica
2022 Volume 47, Issue 2, Page(s) 492–498
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 ... ...
| 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. |
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| MeSH term(s) | Animals ; Atherosclerosis/drug therapy ; Atherosclerosis/genetics ; Lipoproteins, LDL/metabolism ; Mice ; MicroRNAs/genetics ; MicroRNAs/metabolism ; Proprotein Convertase 9/genetics ; Proprotein Convertase 9/metabolism ; Receptors, LDL/genetics ; Receptors, LDL/metabolism ; Saponins ; Signal Transduction ; Triterpenes |
| Chemical Substances | Lipoproteins, LDL ; MicroRNAs ; Mirn17 microRNA, mouse ; Receptors, LDL ; Saponins ; Triterpenes ; VLDL receptor ; astragaloside A (3A592W8XKE) ; Pcsk9 protein, mouse (EC 3.4.21.-) ; Proprotein Convertase 9 (EC 3.4.21.-) |
| Language | Chinese |
| Publishing date | 2022-02-17 |
| Publishing country | China |
| Document type | Journal Article |
| ZDB-ID | 1004649-5 |
| ISSN | 1001-5302 ; 0254-0029 |
| ISSN | 1001-5302 ; 0254-0029 |
| DOI | 10.19540/j.cnki.cjcmm.20210918.701 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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