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千层纸素A改善大鼠慢性心力衰竭的作用及其分子机制

Oroxylin A ameliorates isoproterenol-induced heart failure model in rats through promoting myocardial autophagy

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【作者】 王晶晶田晨光张金盈张继佳吴照科

【Author】 WANG Jingjing;TIAN Chenguang;ZHANG Jinying;ZHANG Jijia;WU Zhaoke;Department of Hypertension,the First Provincial Hospital of Henan Provincial People’s Hospital;Department of Endocrinology,the Second Affiliated Hospital of Zhengzhou University;Department of Cardiovascular,the First Affiliated Hospital of Zhengzhou University;Department of Gerontology,the Second Affiliated Hospital of Zhengzhou University;

【通讯作者】 吴照科;

【机构】 河南省人民医院省直第一医院高血压科郑州大学第二附属医院内分秘科郑州大学第一附属医院心血管内科郑州大学第二附属医院老年医学科

【摘要】 探讨千层纸素A(oroxylin A,OA)对异丙肾上腺素诱导的大鼠心力衰竭的保护作用及其分子机制。与模型组相比,OA给药组[25、50、100 mg/(kg·d),每组8只大鼠,灌胃给药8周]可剂量依赖地改善大鼠心力衰竭的症状,血流动力学参数和心脏射血分数有较大改善,心脏功能指数明显恢复,心脏彩超及苏木精-伊红染色、Masson染色提示心脏损伤程度明显减轻,多种神经内分泌因子如去甲肾上腺素、醛固酮、脑钠肽等在OA给药组均显著下调。进一步利用大鼠原代心肌细胞发现,OA可通过抑制AKT1-RPS6KB1信号通路促进心肌细胞自噬。实验结果表明,OA可通过促进心肌细胞的自噬来改善异丙肾上腺素所诱导的大鼠心力衰竭。

【Abstract】 The protective effect and mechanism of Oroxylin A,a naturally occurring compound in Scutellaria baicalensis Georgi,was investigated in this study. Isoproterenol administration to rats triggered classic cardiac failure,as demonstrated by objective parameters of cardiac dysfunction. Intragastric administration of oroxylin A at the dose of 25,50 and 100 mg/( kg·d) significantly improved deranged cardiac parameters in the isoproterenolinduced heart failure model in a dose-dependent manner. At the same time,oroxylin A markedly ameliorated cardiac histological changes and down-regulated serum levels of various neuroendocrine factors including norepinephrine,aldosterone,brain natriuretic peptide,endothelin 1,angiotensin Ⅱ and so on. Mechanistically,augmenting autophagy of myocardial cells via the inhibition of AKT1-RPS6 KB1 signaling contributed to the improvement of isoproterenol-induced rat heart failure by oroxylin A. Taken together,these results suggest that oroxylin A ameliorates heart failure through promoting autophagy in myocardial cells.

【基金】 国家自然科学基金资助项目(No.81570274)~~
  • 【文献出处】 中国药科大学学报 ,Journal of China Pharmaceutical University , 编辑部邮箱 ,2018年06期
  • 【分类号】R285.5
  • 【被引频次】5
  • 【下载频次】246
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