Effect of microRNA-34a/SIRT1/p53 signal pathway on notoginsenoside R₁ delaying vascular endothelial cell senescence.
10.19540/j.cnki.cjcmm.20180110.001
- Author:
Xiao-Hua LAI
1
;
Yan LEI
2
;
Jing YANG
2
;
Cheng-Kui XIU
2
Author Information
1. Guangdong Metabolic Disease Research Center of Integrated Chinese and Western Medicine， Institute of Chinese Medicinal Sciences， Guangdong Pharmaceutical University， Guangzhou 510006， China.
2. Beijing Key Laboratory of Traditional Chinese Medicine Basic Research on Prevention and Treatment of Major Disease， Experimental Research Center， China Academy of Chinese Medical Sciences， Beijing 100700， China.
- Publication Type:Journal Article
- Keywords:
SIRT1;
cell senescence;
microRNA-34a;
notoginsenoside R₁;
p53;
vascular aging;
vascular endothelial cell
- MeSH:
Cells, Cultured;
Cellular Senescence;
drug effects;
Ginsenosides;
pharmacology;
Human Umbilical Vein Endothelial Cells;
Humans;
Hydrogen Peroxide;
MicroRNAs;
genetics;
Signal Transduction;
Sirtuin 1;
genetics;
Tumor Suppressor Protein p53;
genetics
- From:
China Journal of Chinese Materia Medica
2018;43(3):577-584
- CountryChina
- Language:Chinese
-
Abstract:
This study aimed to investigate the effect of notoginsenoside R₁ in delaying H₂O₂-induced vascular endothelial cell senescence through microRNA-34a/SIRT1/p53 signal pathway. In this study， human umbilical vein endothelial cells(HUVECs) were selected as the study object; the aging model induced by hydrogen peroxide(H₂O₂) was established， with resveratrol as the positive drug. HUVECs were randomly divided into four groups， youth group， senescence model group， notoginsenoside R₁ group and resveratrol group. Notoginsenoside R₁ group and resveratrol group were modeled with 100 μmoL·L⁻¹ H₂O₂ for 4 h after 24 h treatment with notoginsenoside R₁(30 μmoL·L⁻¹) and resveratrol(10 μmoL·L⁻¹) respectively. At the end， each group was cultured with complete medium for 24 h. The degree of cellular senescence was detected by senescence-associated β-galactosidase(SA-β-Gal) staining kit， the cell viability was detected by cell counting kit-8， the cell cycle distribution was analyzed by flow cytometry， and the cellular SOD activity was detected by WST-1 method in each group. The expressions of SIRT1， p53， p21 and p16 proteins in HUVECs were detected by Western blot. In addition， the mRNA expressions of miRNA-34a， SIRT1 and p53 in HUVECs were assayed by Real-time PCR. These results indicated that notoginsenoside R₁ significantly reduced the positive staining rate of senescent cells， enhanced the cell proliferation capacity and intracellular SOD activity， decreased the proportion of cells in G₀/G₁ phase， and increased the percentage of cells in S phase simultaneously compared with the senescence model group. Moreover， notoginsenoside R₁ decreased the mRNA expressions of miRNA-34a and p53 and the protein expression of p53， p21 and p16.At the same time， notoginsenoside R₁ increased the protein and mRNA expressions of SIRT1. The differences in these results between the senescence model group and the notoginsenoside R₁ group were statistically significant(<0.05). However， there was not statistically significant difference in these results between the notoginsenoside R₁ group and the resveratrol group. In conclusion， the senescence of endothelial cells induced by H₂O₂ can be used as a model for studying aging. Notoginsenoside R₁ has an obvious anti-aging effect on vascular endothelial cells in this study. The possible mechanism is that notoginsenoside R₁ can delay the senescence process of vascular endothelial cells induced by H₂O₂ by regulating microRNA-34a/SIRT1/p53 signal pathway.
