Astragalus polysaccharide attenuates isoproterenol-induced cardiac hypertrophy by regulating TNF-α/PGC-1α signaling mediated energy biosynthesis

被引:90
作者
Luan, Aina [1 ,2 ]
Tang, Futian [1 ]
Yang, Yuhong [1 ]
Lu, Meili [1 ]
Wang, Hongxin [1 ]
Zhang, Yingjie [2 ]
机构
[1] Liaoning Med Univ, Inst Drug Res, Key Lab Cardiovasc & Cerebrovasc Drug Res Liaonin, Jinzhou 121001, Peoples R China
[2] Liaoning Med Univ, Affiliated Hosp 1, Internal Med Cardiovasc Dept, Jinzhou 121001, Peoples R China
基金
中国国家自然科学基金;
关键词
Astragalus polysaccharide; Cardiac hypertrophy; Hemodynamics; Energy biosynthesis; TNF-alpha/PGC-1 alpha signaling; NF-KAPPA-B; HEART-FAILURE; GLUCOSE-OXIDATION; RAT MODEL; PGC-1-ALPHA; METABOLISM; CALCINEURIN/NFATC3; CARDIOMYOPATHY; CARDIOMYOCYTES; INFLAMMATION;
D O I
10.1016/j.etap.2015.03.014
中图分类号
X [环境科学、安全科学];
学科分类号
083001 [环境科学];
摘要
We previously reported that Astragalus polysaccharide (APS) extracted from Chinese medicine Astragalus membranaceus (Fisch.) Bge, attenuates hypertrophy of neonatal rat ventricular myocytes (NRVMs) induced by isoproterenol (Iso). The present study was designed to investigate the effects and the possible mechanism of APS on Iso-induced hypertrophy in rats and NRVMs with focus on tumor necrosis factor a (TNF-alpha)/peroxisome proliferator-activated receptor-gamma coactivator 1 alpha (PGC-1 alpha) signaling mediated energy biosynthesis. 36-Week old rats were randomly divided into 3 groups: (1) Control, rats received vehicle; (2) Iso, rats received isoproterenol injections; (3) Iso+APS, rats received isoproterenol injections and APS. NRVMs were divided into similar groups as rats. The results showed that combination of APS with Iso significantly attenuated the pathological changes, reduced the ratios of heart weight/body weight (HW/BW) and left ventricular weight/BW (LVW/BW), improved the cardiac hemodynamics, down-regulated mRNA and protein expression of atrial natriuretic peptide (ANP), increased the ratios of ATP/ADP and ATP/AMP, and decreased the content of free fatty acid (FFA) in heart tissue of rats compared with Iso alone. In addition, pretreatment with APS significantly decreased the surface area and protein content, down-regulated mRNA and protein expression of ANP, increased the ratios of ATP/ADP and ATP/AMP, and decreased the content of FFA in NRVMs compared with Iso alone. Furthermore; APS increased the protein expressions of ATP5D, the sigma subunit of ATP synthase, PGC-1 alpha and pyruvate dehydrogenase kinase 4 (PDK4) in tissue and NRVMs respectively and inhibited the production of TNF-alpha in serum and culture medium compared with Iso alone. The results suggested that APS attenuates Iso-induced cardiac hypertrophy through regulating TNF-alpha/PGC-1 alpha signaling mediated energy biosynthesis. (C) 2015 Elsevier B.V. All rights reserved.
引用
收藏
页码:1081 / 1090
页数:10
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