Astragaloside Ⅳ regulates Nrf2/Bach1/HO-1 signaling pathway and inhibits H9c2 cardiomyocyte injury induced by hypoxia-reoxygenation.
10.19540/j.cnki.cjcmm.20190312.001
- Author:
Ping YANG
1
;
Yu-Ping ZHOU
2
;
Xiu-Chun CHANG
1
;
Feng WANG
1
;
Gao-Wen LI
1
Author Information
1. Ningbo College of Health Sciences Ningbo 315100, China.
2. the Affiliated Hospital of Medical School of Ningbo University Ningbo 315020, China.
- Publication Type:Journal Article
- Keywords:
H9c2 cardiomyocyte;
Nrf2/Bach1/HO-1 pathway;
astragaloside Ⅳ;
hypoxia-reoxygenation injury
- MeSH:
Apoptosis;
Basic-Leucine Zipper Transcription Factors;
metabolism;
Cell Hypoxia;
Cells, Cultured;
Heme Oxygenase-1;
metabolism;
Humans;
Myocytes, Cardiac;
drug effects;
NF-E2-Related Factor 2;
metabolism;
Saponins;
pharmacology;
Signal Transduction;
Triterpenes;
pharmacology
- From:
China Journal of Chinese Materia Medica
2019;44(11):2331-2337
- CountryChina
- Language:Chinese
-
Abstract:
Astragaloside Ⅳ(AS-Ⅳ) has protective effects against ischemia-reperfusion injury(IRI), but its mechanism of action has not yet been determined. This study aims to investigate the protective effects and mechanism of AS-Ⅳ on H9c2 cardiomyocyte injury induced by hypoxia-reoxygenation(H/R). The H/R model of myocardial cells was established by hypoxic culture for 12 hours and then reoxygenation culture for 8 hours. After AS-Ⅳ treatment, cell viability, the reactive oxygen species(ROS) levels, as well as the content or activity of superoxide dismutase(SOD), malondialdehyde(MDA), interleukin 6(IL-6), and tumor necrosis factor alpha(TNF-α), were measured to evaluate the effect of AS-Ⅳ treatment. The effect of AS-Ⅳ on HO-1 protein expression and nuclear Nrf2 and Bach1 protein expression was determined by Western blot. Finally, siRNA was used to knock down HO-1 gene expression to observe its reversal effect on AS-Ⅳ intervention. The results showed that as compared with the H/R model group, the cell viability was significantly increased(P<0.01), ROS level in the cells, MDA, hs-CRP and TNF-α in cell supernatant and nuclear protein Bach1 expression in the cells were significantly decreased(P<0.01), while SOD content, HO-1 protein expression in cells and expression of nuclear protein Nrf2 were significantly increased(P<0.01) in H/R+AS-Ⅳ group. However, pre-transfection of HO-1 siRNA into H9c2 cells by liposome could partly reverse the above effects of AS-Ⅳ after knocking down the expression of HO-1. This study suggests that AS-Ⅳ has significant protective effect on H/R injury of H9c2 cardiomyocytes, and Nrf2/Bach1/HO-1 signaling pathway may be a key signaling pathway for the effect.
