Relationship between edaravone-induced inhibition of pressure overload-induced myocardial remodeling and AT1R/MAPKs/StAR signaling pathway in rats
10.3760/cma.j.cn131073.20210409.00527
- VernacularTitle:依达拉奉抑制大鼠压力超负荷致心肌重构形成与AT1R/MAPKs/StAR信号通路的关系
- Author:
Weiwei ZHANG
1
;
Shuzhen YU
;
Lina ZHENG
;
Ting WANG
;
Rongshan LI
Author Information
1. 山西医科大学附属人民医院麻醉科 山西医科大学附属人民医院博士后工作站，太原 030012
- Keywords:
Free radical scavengers;
Ventricular remodeling;
Receptor, angiotensin, type 1;
Mitogen-activated protein kinases;
Steroidogenic acute regulatory protein
- From:
Chinese Journal of Anesthesiology
2021;41(5):625-629
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To evaluate the relationship between edaravone-induced inhibition of pressure overload-induced myocardial remodeling and angiotensin Ⅱ type 1 receptor (AT1R)/mitogen activated protein kinases (MAPKs)/steroidogenic acute regulatory protein (StAR) signaling pathway in rats.Methods:Thirty-six clean-grade healthy male Sprague-Dawley rats, aged 2 months, weighing 200-220 g, were divided into 3 groups ( n=12 each) using a random number table method: sham operation group (S group), pressure overload group (POL group) and edaravone group (E group). The cardiac pressure overload was induced by ligation of thoracic aorta for 8 weeks.After the model preparation, 0.9% sodium chloride 10 ml/kg was intraperitoneally injected daily in group POL, and edaravone 10 mg/kg was given instead in group E for 8 consecutive weeks.After the model was successfully established, the left ventricular ejection fraction (EF) and ventricular shortening fraction (FS) were measured by two-dimensional ultrasound.The animals were sacrificed by bloodletting, and the heart weight/body weight ratio (HW/BW ratio) was calculated.Myocardial tissues were obtained for determination of the cross-sectional area (MSA) after HE staining, the collagen volume fraction (CVF) (using Masson′s staining), the expression of AT1R and StAR (by immunohistochemistry), extracellular signal-regulated kinase 1/2 (ERK1/2) and p38 MAPK phosphorylation levels (p-ERK1/2/ERK1/2 ratio and p-p38 MAPK/p38 MAPK ratio) (by Western blot) and the aldosterone content (by enzyme-linked immunosorbent assay). Results:Compared with group S, the HW/BW ratio, MSA and CVF were significantly increased, EF and FS were decreased, AT1R and StAR expression was up-regulated, and p-ERK1/2/ERK1/2 ratio, p-p38 MAPK/p38 MAPK ratio and aldosterone content were increased in group POL ( P<0.05). Compared with POL group, the HW/BW ratio, MSA and CVF were significantly decreased, EF and FS were increased, AT1R and StAR expression was down-regulated, and p-ERK1/2/ERK1/2 ratio, p-p38 MAPK/p38 MAPK ratio and aldosterone content were decreased in group E ( P<0.05). Conclusion:The mechanism of edaravone-induced inhibition of pressure overload-induced myocardial remodeling is probably associated with inhibiting the activation of AT1R/MAPKs/StAR signaling pathway in rats.
