Curcumin prevents cardiac remodeling secondary to chronic renal failure through deactivation of hypertrophic signaling in rats
Curcumin prevents cardiac remodeling secondary to chronic renal failure through deactivation of hypertrophic signaling in rats
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DOI：
10.1152/ajpheart.00154.2010
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发表时间：
2010-10-01
影响因子：
4.8
通讯作者：
Kukreja, Rakesh C.
中科院分区：
文献类型：
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作者：
Ghosh, Siddhartha S.;Salloum, Fadi N.;Kukreja, Rakesh C.
Ghosh SS，Salloum FN，Abbate A，Krieg R，Sica DA，Gehr TW，Kukreja RC.姜黄素通过抑制肥大信号通路预防慢性肾功能衰竭大鼠心脏重塑。美国生理学杂志心脏循环生理学299：H975-H984，2010年。首次发表于2010年7月2日; doi：10.1152/ajpheart.00154.2010.-慢性肾功能衰竭（CRF）后终末期肾病患者左心室肥厚（LVH）的发生率较高。我们研究了姜黄素（印度咖喱香料姜黄中的主要姜黄素类化合物）在减轻LVH中的治疗效果，并试图描述相关的信号通路在减弱肾切除大鼠的肥大反应中的作用。成年Sprague-Dawley大鼠通过切除5/6的肾脏进行肾切除术（Nx）。4组研究7周：1）对照（假手术），2）Nx，3）Nx +姜黄素（150 mg/kg bid），4）Nx +依那普利（15 mg/kg bid）作为阳性对照。肾次全切除引起肾功能不全，表现为蛋白尿逐渐增加，血尿素氮和血浆肌酐升高。Nx大鼠在吸气时表现出明显的肥大反应和下腔静脉直径增加，姜黄素或依那普利可抑制这种反应。此外，Nx大鼠表现出与肥大反应密切相关的信号分子的变化。这些包括增加的糖原合成酶激酶-3 β磷酸化、β-连环蛋白表达、钙调神经磷酸酶、活化T细胞的磷酸化（p）核因子、pERK和p-cAMP依赖性激酶。姜黄素和依那普利都有效地抑制了这些通路。姜黄素通过抑制多种肥大信号通路减轻肾切除大鼠心肌肥大和重构。考虑到姜黄素的安全性，这些研究将有助于未来抑制CRF患者肥大的临床试验。
Ghosh SS, Salloum FN, Abbate A, Krieg R, Sica DA, Gehr TW, Kukreja RC. Curcumin prevents cardiac remodeling secondary to chronic renal failure through deactivation of hypertrophic signaling in rats. Am J Physiol Heart Circ Physiol 299: H975-H984, 2010. First published July 2, 2010; doi:10.1152/ajpheart.00154.2010.-The prevalence of left ventricular hypertrophy (LVH) is frequent in patients with end-stage renal disease following chronic renal failure (CRF). We investigated the therapeutic efficacy of curcumin, the principal curcuminoid of the Indian curry spice turmeric, in attenuation of LVH and sought to delineate the associated signaling pathways in blunting the hypertrophic response in nephrectomized rats. Adult Sprague-Dawley rats underwent nephrectomy (Nx) by removal of 5/6 of the kidneys. Four groups were studied for 7 wk: 1) control (sham), 2) Nx, 3) Nx + curcumin (150 mg/kg bid), and 4) Nx + enalapril (15 mg/kg bid) as positive control. Subtotal nephrectomy caused renal dysfunction, as evidenced by a gradual increase in proteinuria and elevation in blood urea nitrogen and plasma creatinine. Nx rats showed a significant hypertrophic response and increased diameter of inferior vena cava at inspiration, which was inhibited by treatment with curcumin or enalapril. Moreover, the Nx rats demonstrated changes in the signaling molecules critically involved in the hypertrophic response. These include increased glycogen synthase kinase-3 beta phosphorylation, beta-catenin expression, calcineurin, phosphorylated (p) nuclear factor of activated T cells, pERK, and p-cAMP-dependent kinase. Both curcumin and enalapril variably but effectively deactivated these pathways. Curcumin attenuates cardiac hypertrophy and remodeling in nephrectomized rats through deactivation of multiple hypertrophic signaling pathways. Considering the safety of curcumin, these studies should facilitate future clinical trials in suppressing hypertrophy in patients with CRF.