Abstract：
BACKGROUND: Clinical studies have found that Qianyang Yuyin granule (QYYYG), a kind of oral Chinese patent medicine, had definite clinical effect for hypertensive myocardial remodeling. However, the potential mechanism is not entirely clear.
OBJECTIVE: The purpose of this research was to explore the underlying mechanism QYYYG on the treatment of hypertensive myocardial remodeling.
METHODS: Analysis the transcriptome data from the NCBI public platform GEO database and our study to explore the key pathological change of myocardial tissues in hypertensive mice and the main pathway of QYYYG in treating hypertensive myocardial remodeling. Network pharmacological analysis was used to predict the potential target of QYYYG. The molecular docking and molecular dynamics simulation was used for molecular binding analysis of specific compounds and target proteins. In the experiment in vivo, the effect of QYYYG on hypertensive myocardial remodeling and myocardial mitochondrial dysfunction in hypertensive mice caused by Ang Ⅱ was estimated. In the experiment in vitro, the Ang Ⅱ-induced myocardial remodeling model in H9c2 cells was constructed, and the effect of QYYYG on ameliorating myocardial remodeling and mitochondrial dysfunction was evaluated.
RESULTS: Transcriptome analysis suggested that mitochondrial dysfunction was a key pathological change of myocardial tissues in hypertensive mice, and QYYYG could improve hypertensive myocardial remodeling through enhancing mitochondrial biogenesis to repair myocardial mitochondrial dysfunction. Network pharmacological analysis predicted that SIRT1 was an important potential target of QYYYG in treating hypertensive myocardial remodeling, and basically all the active components, especially quercetin, had a great binding affinity with SIRT1. Experiments in vivo proved that QYYYG had great efficacy hypertensive myocardial remodeling in Ang Ⅱ-treated mice. It was found that QYYYG improved the quality and quantity of mitochondria, and increased SIRT1 levels in myocardial tissue of Ang Ⅱ-treated mice. In Ang Ⅱ-treated H9c2 cells, with intervention of QYYYG, myocardial remodeling and myocardial mitochondrial dysfunction was ameliorated. In addition, QYYYG up-regulated SIRT1 expression and enhanced mitochondrial biogenesis in Ang Ⅱ-treated H9c2 cells.
CONCLUSIONS: This study suggested that mitochondrial dysfunction was an important pathological change of myocardial tissues in hypertensive mice. QYYYG might ameliorate the mitochondrial dysfunction of hypertensive myocardial remodeling through up-regulating SIRT1 expression to enhance the mitochondrial biogenesis.
OBJECTIVE: The purpose of this research was to explore the underlying mechanism QYYYG on the treatment of hypertensive myocardial remodeling.
METHODS: Analysis the transcriptome data from the NCBI public platform GEO database and our study to explore the key pathological change of myocardial tissues in hypertensive mice and the main pathway of QYYYG in treating hypertensive myocardial remodeling. Network pharmacological analysis was used to predict the potential target of QYYYG. The molecular docking and molecular dynamics simulation was used for molecular binding analysis of specific compounds and target proteins. In the experiment in vivo, the effect of QYYYG on hypertensive myocardial remodeling and myocardial mitochondrial dysfunction in hypertensive mice caused by Ang Ⅱ was estimated. In the experiment in vitro, the Ang Ⅱ-induced myocardial remodeling model in H9c2 cells was constructed, and the effect of QYYYG on ameliorating myocardial remodeling and mitochondrial dysfunction was evaluated.
RESULTS: Transcriptome analysis suggested that mitochondrial dysfunction was a key pathological change of myocardial tissues in hypertensive mice, and QYYYG could improve hypertensive myocardial remodeling through enhancing mitochondrial biogenesis to repair myocardial mitochondrial dysfunction. Network pharmacological analysis predicted that SIRT1 was an important potential target of QYYYG in treating hypertensive myocardial remodeling, and basically all the active components, especially quercetin, had a great binding affinity with SIRT1. Experiments in vivo proved that QYYYG had great efficacy hypertensive myocardial remodeling in Ang Ⅱ-treated mice. It was found that QYYYG improved the quality and quantity of mitochondria, and increased SIRT1 levels in myocardial tissue of Ang Ⅱ-treated mice. In Ang Ⅱ-treated H9c2 cells, with intervention of QYYYG, myocardial remodeling and myocardial mitochondrial dysfunction was ameliorated. In addition, QYYYG up-regulated SIRT1 expression and enhanced mitochondrial biogenesis in Ang Ⅱ-treated H9c2 cells.
CONCLUSIONS: This study suggested that mitochondrial dysfunction was an important pathological change of myocardial tissues in hypertensive mice. QYYYG might ameliorate the mitochondrial dysfunction of hypertensive myocardial remodeling through up-regulating SIRT1 expression to enhance the mitochondrial biogenesis.
摘要：
背景：临床研究发现，千阳育阴颗粒（QYYYG），一种口服中成药，对高血压心肌重构有一定的临床疗效。然而,潜在的机制尚不完全清楚。
目的：本研究的目的是探讨QYYYG治疗高血压心肌重构的潜在机制。
方法：分析NCBI公共平台GEO数据库和本研究的转录组数据，探讨高血压小鼠心肌组织的关键病理变化和QYYYG治疗高血压心肌重构的主要途径。网络药理学分析用于预测QYYYG的潜在靶标。分子对接和分子动力学模拟用于特定化合物和靶蛋白的分子结合分析。在体内实验中，评价QYYYG对AngⅡ引起的高血压小鼠心肌重构和心肌线粒体功能障碍的影响。在体外实验中，构建AngⅡ诱导H9c2细胞心肌重构模型,并评价QYYYG改善心肌重塑和线粒体功能障碍的作用。
结果：转录组分析提示线粒体功能障碍是高血压小鼠心肌组织的关键病理变化，QYYYG可以通过增强线粒体生物合成来修复心肌线粒体功能障碍，从而改善高血压心肌重塑。网络药理学分析预测SIRT1是QYYYG治疗高血压心肌重构的重要潜在靶点,基本上所有的活性成分，尤其是槲皮素,与SIRT1有很大的结合亲和力。体内实验证明，QYYYG对AngⅡ治疗小鼠的高血压心肌重塑有很大疗效。发现QYYYG提高了线粒体的质量和数量，AngⅡ处理小鼠心肌组织SIRT1水平升高。在AngⅡ处理的H9c2细胞中，在QYYYG的干预下，心肌重塑和心肌线粒体功能障碍得到改善。此外,QYYYG上调AngⅡ处理的H9c2细胞SIRT1表达并增强线粒体生物合成.
结论：本研究提示线粒体功能障碍是高血压小鼠心肌组织的重要病理变化。QYYYG可能通过上调SIRT1表达以增强线粒体生物发生来改善高血压心肌重构的线粒体功能障碍。
目的：本研究的目的是探讨QYYYG治疗高血压心肌重构的潜在机制。
方法：分析NCBI公共平台GEO数据库和本研究的转录组数据，探讨高血压小鼠心肌组织的关键病理变化和QYYYG治疗高血压心肌重构的主要途径。网络药理学分析用于预测QYYYG的潜在靶标。分子对接和分子动力学模拟用于特定化合物和靶蛋白的分子结合分析。在体内实验中，评价QYYYG对AngⅡ引起的高血压小鼠心肌重构和心肌线粒体功能障碍的影响。在体外实验中，构建AngⅡ诱导H9c2细胞心肌重构模型,并评价QYYYG改善心肌重塑和线粒体功能障碍的作用。
结果：转录组分析提示线粒体功能障碍是高血压小鼠心肌组织的关键病理变化，QYYYG可以通过增强线粒体生物合成来修复心肌线粒体功能障碍，从而改善高血压心肌重塑。网络药理学分析预测SIRT1是QYYYG治疗高血压心肌重构的重要潜在靶点,基本上所有的活性成分，尤其是槲皮素,与SIRT1有很大的结合亲和力。体内实验证明，QYYYG对AngⅡ治疗小鼠的高血压心肌重塑有很大疗效。发现QYYYG提高了线粒体的质量和数量，AngⅡ处理小鼠心肌组织SIRT1水平升高。在AngⅡ处理的H9c2细胞中，在QYYYG的干预下，心肌重塑和心肌线粒体功能障碍得到改善。此外,QYYYG上调AngⅡ处理的H9c2细胞SIRT1表达并增强线粒体生物合成.
结论：本研究提示线粒体功能障碍是高血压小鼠心肌组织的重要病理变化。QYYYG可能通过上调SIRT1表达以增强线粒体生物发生来改善高血压心肌重构的线粒体功能障碍。
