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人参皂苷Rg(1)抑制腹主动脉缩窄诱导的大鼠左心室肥厚:钙调神经磷酸酶和丝裂原活化蛋白激酶信号通路的参与

Ginsenoside Rg(1) inhibits rat left ventricular hypertrophy induced by abdominal aorta coarctation: involvement of calcineurin and mitogen-activated protein kinase signalings.

作者信息

Deng Jiang, Lv Xin-Tong, Wu Qin, Huang Xie-Nan

机构信息

Department of Pharmacology, Zunyi Medical College, Zunyi, Guizhou, PR China.

出版信息

Eur J Pharmacol. 2009 Apr 17;608(1-3):42-7. doi: 10.1016/j.ejphar.2009.01.048.

Abstract

Ginsenoside Rg(1) (Rg(1)), one of the active components of Panax ginseng, has been reported to inhibit proliferation of vascular smooth muscle cells induced by tumor necrosis factor-alpha. This study aims to investigate whether Rg(1) has protective effect on rat left ventricular hypertrophy and to probe its protective mechanisms. The rat left ventricular hypertrophy was induced by abdominal aorta coarctation and Rg(1) (3.75, 7.5 and 15 mg/kg/day) was given the day after surgery for 21 consecutive days. The left ventricular hypertrophy induced by abdominal aorta coarctation was evidenced by histopathology, electromicroscopy, and by determining the elevated left ventricular weight and the expression of atrial natriuretic peptide. Rg(1) significantly ameliorated left ventricular hypertrophy induced by abdominal aorta coarctation in a dose-dependent manner. To examine the mechanism of protection, the expressions of calcineurin, CnA (the catalytic subunit of calcineurin), extracellular signal-regulated kinase-1, and mitogen-activated protein (MAP) kinase phosphatase-1 were determined at the transcript and protein levels. The abdominal aorta coarctation induced increases in calcineurin, CnA, and extracellular signal-regulated kinase-1 expressions were suppressed, but the expression of MAP kinase phosphatase-1 was increased by Rg(1). These results demonstrate that Rg(1) alleviates left ventricular hypertrophy induced by abdominal aorta coarctation, and the protection appears to be due, at least in part, to its inhibitory effects on calcineurin and MAP kinase signaling pathways.

摘要

人参皂苷Rg(1)(Rg(1))是人参的活性成分之一,据报道它能抑制肿瘤坏死因子-α诱导的血管平滑肌细胞增殖。本研究旨在探讨Rg(1)对大鼠左心室肥厚是否具有保护作用,并探究其保护机制。通过腹主动脉缩窄诱导大鼠左心室肥厚,术后次日给予Rg(1)(3.75、7.5和15毫克/千克/天),连续给药21天。通过组织病理学、电子显微镜检查以及测定左心室重量增加和心房利钠肽表达,证实了腹主动脉缩窄诱导的左心室肥厚。Rg(1)以剂量依赖的方式显著改善了腹主动脉缩窄诱导的左心室肥厚。为了研究保护机制,在转录水平和蛋白质水平测定了钙调神经磷酸酶、CnA(钙调神经磷酸酶的催化亚基)、细胞外信号调节激酶-1和丝裂原活化蛋白(MAP)激酶磷酸酶-1的表达。腹主动脉缩窄诱导的钙调神经磷酸酶、CnA和细胞外信号调节激酶-1表达增加受到抑制,但Rg(1)使MAP激酶磷酸酶-1的表达增加。这些结果表明,Rg(1)减轻了腹主动脉缩窄诱导的左心室肥厚,并且这种保护作用至少部分归因于其对钙调神经磷酸酶和MAP激酶信号通路的抑制作用。

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