黄芪多糖通过调节 TNF-α/PGC-1α 信号转导介导的能量合成来减轻异丙肾上腺素诱导的心肌肥厚。
Astragalus polysaccharide attenuates isoproterenol-induced cardiac hypertrophy by regulating TNF-α/PGC-1α signaling mediated energy biosynthesis.
机构信息
Key Laboratory of Cardiovascular and Cerebrovascular Drug Research of Liaoning Province, Drug Research Institute, Liaoning Medical University, No. 40, Section 3, Songpo Road, Jinzhou 121001, PR China; Internal Medicine-Cardiovascular Department, The First Affiliated Hospital of Liaoning Medical University, No. 2, Section 5, Renming Jie, Jinzhou 121001, PR China.
Key Laboratory of Cardiovascular and Cerebrovascular Drug Research of Liaoning Province, Drug Research Institute, Liaoning Medical University, No. 40, Section 3, Songpo Road, Jinzhou 121001, PR China.
出版信息
Environ Toxicol Pharmacol. 2015 May;39(3):1081-90. doi: 10.1016/j.etap.2015.03.014. Epub 2015 Mar 31.
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 α (TNF-α)/peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α) 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 σ subunit of ATP synthase, PGC-1α and pyruvate dehydrogenase kinase 4 (PDK4) in tissue and NRVMs respectively and inhibited the production of TNF-α in serum and culture medium compared with Iso alone. The results suggested that APS attenuates Iso-induced cardiac hypertrophy through regulating TNF-α/PGC-1α signaling mediated energy biosynthesis.
我们之前报道过，从中药黄芪（膜荚黄芪）中提取的黄芪多糖（APS）可减轻异丙肾上腺素（Iso）诱导的新生大鼠心室肌细胞（NRVM）肥大。本研究旨在探讨 APS 对 Iso 诱导的大鼠和 NRVM 肥大的影响及其可能的机制，重点关注肿瘤坏死因子 α（TNF-α）/过氧化物酶体增殖物激活受体-γ 共激活因子 1α（PGC-1α）信号转导介导的能量合成。36 周龄大鼠随机分为 3 组：（1）对照组，大鼠给予载体；（2）Iso 组，大鼠给予异丙肾上腺素注射；（3）Iso+APS 组，大鼠给予异丙肾上腺素注射和 APS。NRVM 也分为与大鼠相似的组。结果表明，APS 与 Iso 联合应用可显著减轻病理变化，降低心脏重量/体重（HW/BW）和左心室重量/体重（LVW/BW）比值，改善心脏血流动力学，下调心房利钠肽（ANP）mRNA 和蛋白表达，增加 ATP/ADP 和 ATP/AMP 比值，降低心脏组织游离脂肪酸（FFA）含量与 Iso 单独应用相比。此外，APS 预处理可显著降低 ANP 的表面积和蛋白含量，下调 mRNA 和蛋白表达，增加 NRVM 中 ATP/ADP 和 ATP/AMP 比值，降低游离脂肪酸（FFA）含量与 Iso 单独应用相比。此外，APS 分别增加了组织和 NRVM 中 ATP5D、ATP 合酶σ亚基、PGC-1α 和丙酮酸脱氢酶激酶 4（PDK4）的蛋白表达，并抑制了 Iso 单独作用时血清和培养基中 TNF-α的产生。结果表明，APS 通过调节 TNF-α/PGC-1α 信号转导介导的能量合成，减轻 Iso 诱导的心肌肥大。
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