Acacetin improves endothelial dysfunction and aortic fibrosis in insulin-resistant SHR rats by estrogen receptors
- PDF / 3,192,708 Bytes
- 20 Pages / 595.276 x 790.866 pts Page_size
- 29 Downloads / 165 Views
ORIGINAL ARTICLE
Acacetin improves endothelial dysfunction and aortic fibrosis in insulin‑resistant SHR rats by estrogen receptors Yaxin Wei1 · Peipei Yuan1 · Qi Zhang1 · Yang Fu1 · Ying Hou1 · Liyuan Gao1 · Xiaoke Zheng1 · Weisheng Feng1 Received: 8 May 2020 / Accepted: 28 August 2020 © The Author(s) 2020
Abstract The aim of the work was to investigate the effects of acacetin on endothelial dysfunction and aortic fibrosis in insulinresistant SHR rats and explore its mechanism. Seven-week-old male spontaneously hypertensive rats (SHR) were selected to establish a rat model of hypertension with insulin resistance induced by 10% fructose. The nuclear factor kappa B p65 (NF-κB p65) and Collagen I were observed by Immunohistochemistry. Immunofluorescence was used to observe estrogen receptor-alpha (ERα), estrogen receptor-beta (ERβ), and G protein-coupled receptor 30 (GPR30). Western blotting was used to detect interleukin (IL-1β), Arginase 2 (ARG2), Nostrin, endothelial nitric oxide synthase (eNOS), TGF-β, Smad3, ERK pathway proteins such as p-c-Raf, p-MEK1/2, p-ERK, ERK, p-P90RSK and p-MSK1. We found that acacetin did have an improvement on endothelial dysfunction and fibrosis. Meanwhile, it was also found to have a significant effect on the level of estrogen in this model by accident. Then, the experiment of uterine weight gain in mice confirmed that acacetin had a certain estrogen-like effect in vivo and played its role through the estrogen receptors pathway. In vitro experience HUVEC cells were stimulated with 30 mM/L glucose and 100 mM/L NaCl for 24 h to establish the endothelial cell injury model. HUVEC cells were treated with 1 μM/L estrogen receptors antagonist (ICI 182780) for 30 min before administration. Cell experiments showed that acacetin could reduce the apoptosis of HUVEC cells, the levels of inflammatory cytokines and the expression of TGF-β, Collagen I and Smad3 in endothelial cell injury model. After treatment with ICI 182780, the improvement of acacetin was significantly reversed. The results showed that acacetin relieved endothelial dysfunction and reduced the aortic fibrosis in insulin-resistant SHR rats by reducing the release of inflammatory factors and improving vasodilatory function through estrogen signaling pathway. Keywords Acacetin · Endothelial dysfunction · Aortic fibrosis · Estrogen receptors
Introduction Hypertension is a major public health problem in the world, endangering people’s life and health. According to the recently published China cardiovascular disease news 2018, there are currently about 245 million patients with hypertension in China. The prevalence rate in adults is as high as 23.2% and the incidence of insulin resistance in patients Yaxin Wei and Peipei Yuan have contributed equally to this work. * Xiaoke Zheng [email protected] * Weisheng Feng [email protected] 1
Henan University of Chinese Medicine, Zhengzhou 450046, China
with hypertension is as high as 30% to 50% [1]. Patients with hypertension and insulin resistance have a significantly increased ri
Data Loading...
