School of Public Health, Xinjiang Medical University, Urumqi, Xinjiang, China (mainland).
Changsha First Hospital, Changsha, Hunan, China (mainland).
Med Sci Monit. 2018 Sep 10;24:6322-6330. doi: 10.12659/MSM.908912.
BACKGROUND Dracocephalum heterophyllum Benth flavonoid (DHBF) is a Tibetan and Uighur traditional medicine used to treat various disorders such as hypertension, lung heat, cough, and bronchitis; it has good antioxidant activity. Previous studies have shown that DHBF can reduce blood pressure in renovascular hypertensive rats, improve left ventricular systolic and diastolic function, and improve myocardial contractility. Therefore, we aimed to study the effect of DHBF on cardiomyocyte hypertrophy in cultured cells. MATERIAL AND METHODS Neonatal rat cardiomyocytes were cultured, and hypertrophy was induced by angiotensin II (Ang II), with or without varying concentrations of the DHBF extract. Cell Counting Kit-8 assay was used to assess cell viability, RT-qPCR was used to determine mRNA levels, confocal laser scanning microscopy was used to measure cell surface area and intracellular Ca2+ concentrations ([Ca2+]i), and colorimetric assays were used to assess nitric oxide (NO) levels and nitric oxide synthase (NOS) activity. RESULTS Ang II treatment of cardiomyocytes reduced cell viability to ~75% that of controls. Ang II treatment also increased cell surface area; increased mRNA expression of c-jun, atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and β-myosin heavy chain (β-MHC); increased [Ca2+]i; and reduced NOS activity and NO production. DHBF treatment could reverse these effects in a concentration-dependent manner. CONCLUSIONS These results showed that DHBF can ameliorate cardiomyocyte hypertrophy induced by Ang II, as indicated by the downregulation of cardiac hypertrophy genes (ANP, BNP, and β-MHC) and reduction in cell surface area. The mechanism may be related to NO release and [Ca2+]I regulation.
藏药和维吾尔药龙头草总黄酮（DHBF）用于治疗高血压、肺热、咳嗽和支气管炎等多种疾病，具有良好的抗氧化活性。先前的研究表明，DHBF 可降低肾血管性高血压大鼠的血压，改善左心室收缩和舒张功能，提高心肌收缩力。因此，我们旨在研究 DHBF 对培养细胞中心肌细胞肥大的影响。
培养新生大鼠心肌细胞，用血管紧张素 II（Ang II）诱导肥大，同时用或不用不同浓度的 DHBF 提取物。细胞计数试剂盒-8 法评估细胞活力，实时定量 PCR 法测定 mRNA 水平，共聚焦激光扫描显微镜法测量细胞表面积和细胞内 Ca2+浓度([Ca2+]i)，比色法测定一氧化氮（NO）水平和一氧化氮合酶（NOS）活性。
Ang II 处理心肌细胞可使细胞活力降至对照的约 75%。Ang II 处理还增加了细胞表面积；增加了原癌基因 c-jun、心房利钠肽（ANP）、脑利钠肽（BNP）和β-肌球蛋白重链（β-MHC）的 mRNA 表达；增加了 [Ca2+]i；并降低了 NOS 活性和 NO 产生。DHBF 以浓度依赖的方式处理可逆转这些作用。
这些结果表明，DHBF 可改善 Ang II 诱导的心肌细胞肥大，表现为心脏肥大基因（ANP、BNP 和 β-MHC）下调和细胞表面积减小。其机制可能与 NO 释放和[Ca2+]I 调节有关。
