Astragaloside IV Prevents Cardiac Remodeling in the Apolipoprotein E-Deficient Mice by Regulating Cardiac Homeostasis and Oxidative Stress

Cellular Physiology and Biochemistry

Zhi-Ping Bian¹  Chun-Rong Gu¹  Yan-Zi Ding¹  Xiang-Jian Chen¹  Xiong-Zhi Li²  Jin-Dan Xu³  Heng-Fang Wu³  Di Yang³ 

[1] a;a,c;b

关键词: Hypercholesterolemia;    Astragaloside IV;    Cardiac remodeling;    Tissue homeostasis;    Oxidative stress;   

DOI  :  10.1159/000486166

学科分类：分子生物学，细胞生物学和基因

来源: S Karger AG

【 摘 要 】

Background Hypercholesterolemia is a risk factor for the development of cardiac hypertrophy. Astragaloside IV (AST-IV) possesses cardiovascular protective properties. We hypothesize that AST-IV prevents cardiac remodeling with hypercholesterolemia via modulating tissue homeostasis and alleviating oxidative stress. Methods The ApoE^-/- mice were treated with AST-IV at 1 or 10 mg/kg for 8 weeks. The blood lipids tests, echocardiography, and TUNEL were performed. The mRNA expression profile was detected by real-time PCR. The myocytes size and number, and the expressions of proliferation (ki67), senescence (p16^INK4a), oxidant (NADPH oxidase 4, NOX4) and antioxidant (superoxide dismutase, SOD) were observed by immunofluorescence staining. Results Neither 1 mg/kg nor 10 mg/kg AST-IV treatment could decrease blood lipids in ApoE^-/- mice. However, the decreased left ventricular ejection fraction (LVEF) and fractional shortening (FS) in ApoE^–/– mice were significantly improved after AST-IV treatment. The cardiac collagen volume fraction declined nearly in half after AST-IV treatment. The enlarged myocyte size was suppressed, and myocyte number was recovered, and the alterations of genes expressions linked to cell cycle, proliferation, senescence, p53-apoptosis pathway and oxidant-antioxidants in the hearts of ApoE^-/- mice were reversed after AST-IV treatment. The decreased ki67 and increased p16^INK4a in the hearts of ApoE^-/- mice were recovered after AST-IV treatment. The percentages of apoptotic myocytes and NOX4-positive cells in AST-IV treated mice were decreased, which were consistent with the gene expressions. Conclusion AST-IV treatment could prevent cardiac remodeling and recover the impaired ventricular function induced by hypercholesterolemia. The beneficial effect of AST-IV might partly be through regulating cardiac homeostasis and anti-oxidative stress.

【 授权许可】

CC BY-NC-ND