Astragaloside IV protects against isoproterenol-induced cardiac hypertrophy by regulating NF-κB/PGC-1α signaling mediated energy biosynthesis.
Astragaloside IV protects against isoproterenol-induced cardiac hypertrophy by regulating NF-κB/PGC-1α signaling mediated energy biosynthesis.
复制标题
DOI：
10.1371/journal.pone.0118759
复制
发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Wang H
中科院分区：
文献类型：
--
作者：
Zhang S;Tang F;Yang Y;Lu M;Luan A;Zhang J;Yang J;Wang H
我们曾报道黄芪（Astragalus membranaceus，菲施）的主要活性成分黄芪甲苷（Astragaloside IV，ASIV）对异丙肾上腺素（Iso）诱导的大鼠心肌肥厚有保护作用，但其机制尚不清楚。心肌能量合成障碍导致心肌肥厚，核因子-κB（NF-κB B）/过氧化物酶体激活受体-γ辅激活因子1α（PGC-1α）信号通路参与了心肌能量合成障碍。本研究从NF-κB/PGC-1α信号通路介导的能量合成途径探讨ASIV改善心肌肥厚的机制。用Iso单独或与ASIV组合处理Sprague-Dawley（SD）大鼠或新生大鼠心室肌细胞（NRVM）。结果显示，ASIV联合用药可明显减轻心肌病理改变，降低心脏重量/体重比、左心室重量/体重比，改善心脏血流动力学，下调心钠素（ANP）、脑钠素（BNP）mRNA表达，提高ATP/AMP比值，降低心肌组织游离脂肪酸（FFA）含量。ASIV预处理可降低NRVM的表面积和蛋白含量，下调ANP和BNP的mRNA表达，增加ATP/AMP比值，降低FFA含量。与Iso单用相比，ASIV可增加大鼠和NRVM中ATP合酶亚基ATP 5D和PGC-1α的蛋白表达，抑制NF-κB B亚基p65向核内转位。p65特异性抑制剂Parthenoprotein（Par）在NRVM中发挥与ASIV相似的作用。与单独使用Iso相比，siRNA敲除p65可降低NRVM的表面积并增加PGC-1α的表达。结果提示，ASIV通过调节NF-κB/PGC-1α信号通路介导的能量生物合成，对Iso诱导的心肌肥厚具有保护作用。
We previously reported that Astragaloside IV (ASIV), a major active constituent of Astragalus membranaceus (Fisch) Bge protects against cardiac hypertrophy in rats induced by isoproterenol (Iso), however the mechanism underlying the protection remains unknown. Dysfunction of cardiac energy biosynthesis contributes to the hypertrophy and Nuclear Factor κB (NF-κB)/Peroxisome Proliferator-Activated Receptor-γ Coactivator 1α (PGC-1α) signaling gets involved in the dysfunction. The present study was designed to investigate the mechanism by which ASIV improves the cardiac hypertrophy with focuses on the NF-κB/PGC-1α signaling mediated energy biosynthesis. Sprague-Dawley (SD) rats or Neonatal Rat Ventricular Myocytes (NRVMs) were treated with Iso alone or in combination with ASIV. The results showed that combination with ASIV significantly attenuated the pathological changes, reduced the ratios of heart weight/body weight and Left ventricular weight/body weight, improved the cardiac hemodynamics, down-regulated mRNA expression of Atrial Natriuretic Peptide (ANP) and Brain Natriuretic Peptide (BNP), increased the ratio of ATP/AMP, and decreased the content of Free Fat Acid (FFA) in heart tissue of rats compared with Iso alone. In addition, pretreatment with ASIV significantly decreased the surface area and protein content, down-regulated mRNA expression of ANP and BNP, increased the ratio of ATP/AMP, and decreased the content of FFA in NRVMs compared with Iso alone. Furthermore, ASIV increased the protein expression of ATP5D, subunit of ATP synthase and PGC-1α, inhibited translocation of p65, subunit of NF-κB into nuclear fraction in both rats and NRVMs compared with Iso alone. Parthenolide (Par), the specific inhibitor of p65, exerted similar effects as ASIV in NRVMs. Knockdown of p65 with siRNA decreased the surface areas and increased PGC-1α expression of NRVMs compared with Iso alone. The results suggested that ASIV protects against Iso-induced cardiac hypertrophy through regulating NF-κB/PGC-1α signaling mediated energy biosynthesis.
登录
查看更多内容
DOI：
10.1046/j.1440-1681.2002.03655.x
发表时间：
2002-04-01
影响因子：
2.9
作者：
Lehman, JJ;Kelly, DP
通讯作者：
Kelly, DP
影响因子：
10.8
作者：
Alvarez-Guardia, David;Palomer, Xavier;Vazquez-Carrera, Manuel
通讯作者：
Vazquez-Carrera, Manuel
影响因子：
--
作者：
ALLARD, MF;SCHONEKESS, BO;LOPASCHUK, GD
通讯作者：
LOPASCHUK, GD
影响因子：
37.8
作者：
KAGAYA, Y;KANNO, Y;TAKISHIMA, T
通讯作者：
TAKISHIMA, T
影响因子：
4.8
作者：
UNVERFERTH, DV;LEE, SW;WALLICK, ET
通讯作者：
WALLICK, ET