The protective effects of Astragaloside Ⅳ on diastolic function of rat thoracic aortic rings impaired by microvesicles.
10.12047/j.cjap.5659.2018.040
- Author:
Ye-Yi LI
1
;
Man SHANG
1
;
Kun-Wei ZHANG
1
;
Su WEI
1
;
Chao LIU
1
;
Qian ZHU
1
;
Jun-Yu ZHAO
1
;
Yan-Na WU
1
;
Jun-Qiu SONG
1
;
Yan-Xia LIU
1
Author Information
1. Department of Pharmacology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China.
- Publication Type:Journal Article
- Keywords:
Astragaloside IV;
HUVECs;
aortic rings;
hypoxia/reoxygenation;
microvesicles;
rats
- MeSH:
Animals;
Aorta, Thoracic;
drug effects;
Cell-Derived Microparticles;
pathology;
Human Umbilical Vein Endothelial Cells;
Humans;
In Vitro Techniques;
MAP Kinase Signaling System;
Male;
Nitric Oxide;
metabolism;
Nitric Oxide Synthase Type III;
metabolism;
Proto-Oncogene Proteins c-akt;
metabolism;
Rats;
Rats, Wistar;
Saponins;
pharmacology;
Triterpenes;
pharmacology;
Vasodilation
- From:
Chinese Journal of Applied Physiology
2018;34(2):164-168
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVES:To investigate the effects of Astragaloside IV (AST) on diastolic function of rat thoracic aorta rings which was injured by microvesicles derived from hypoxia/reoxygenation (H/R)-treated human umbilical vein endothelial cells (HUVECs), and the mechanism of AST.
METHODS:H/R-induced endothelial microvesicles (H/R-EMVs) were generated from cultured HUVECs under the condition of hypoxia for 12 hour/Reoxygenation for 4 hour, H/R-EMVs were stored in D-Hank's solution. Male Wistar rats were underwent thoracotomy, the thoracic aorta with intact endothelium were carefully removed and cut into 3~4 mm rings. The experiment was divided into six groups. H/R-EMVs group:thoracic aortic rings of rats were incubated in culture medium and treated with H/R-EMVs in a final concentration of 10g/ml; different doses of AST groups:thoracic aortic rings of rats were treated with 10, 20, 40, 60 mg/L AST co-incubated with 10g/ml H/R-EMVs respectively; control group were treated with the same volume of D-Hank's solution. Duration of incubation was 4 h, each group was tested in five replicate aortic rings. Effects of AST on endothelium-dependent relaxation were detected. The production of nitric oxide (NO) and the level of endothelial NO synthase (eNOS), phosphorylated eNOS (p-eNOS, Ser-1177), serine/threonine kinase (Akt), phosphorylated Akt (p-Akt, Ser-473), extracellular regulated protein kinases (ERK1/2) and phosphorylated ERK1/2 (p-ERK1/2, Thr202/Tyr204) of rat thoracic aortic rings were detected.
RESULTS:Teng/ml H/R-EMVs could impaire the relaxation of rat thoracic aortic rings significantly (<0.01). Compared with H/R-EMVs group, relaxation of rat thoracic aortic rings was increased by 20, 40 and 60 mg/L AST in a concentration-dependent manner (<0.01), the level of NO production was also enhanced (<0.05, <0.01). The level of t-eNOS, t-Akt and ERK1/2 was not changed, but the level of p-eNOS, p-Akt and p-ERK1/2 increased by the treatment with AST (<0.01).
CONCLUSIONS:AST could effectively ameliorate endotheliumdependent relaxation of rat thoracic aortic rings impaired by H/R-EMVs in a concentration-dependent manner, the mechanism might involve the increase in production of NO, and the protein level of p-eNOS, p-Akt and p-ERK1/2.
