Li Xue-Qin, Lu Shuang, Xia Lei, Shan Xiao-Li, Zhao Wen-Xia, Chen Hui-Hua, Zhang Chen, Guo Wei, Xu Ming, Lu Rong, Zhao Pei
School of Basic Medical Science, Shanghai University of Traditional Chinese Medicine Shanghai, China.
Yueyang Hospital of Integrative Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine China.
Am J Transl Res. 2022 Jun 15;14(6):3840-3853. eCollection 2022.
Stachydrine hydrochloride (Sta), an activated alkaloid, is isolated from traditional Chinese medicine Yimucao. In previous studies, the cardioprotective effects of Sta were found in our laboratory. However, the underling mechanisms of Sta is not fully elucidated. The aim of this study was to provide a detailed account of the anti-hypertrophic effects of Sta on transcriptional regulation. In vivo, C57BL/6J mice were subjected to transverse aortic constriction (TAC) and were orally treated with Sta. Morphological assessments, echocardiographic parameters, histological analyses and immunofluorescence were used to evaluate cardiac hypertrophy. In vitro, cardiomyocytes were stimulated by phenylephrine (PE), and cell surface and hypertrophy markers were tested by immunofluorescence and real-time polymerase chain reaction (RT-PCR). Moreover, western blotting, RT-PCR and luciferase reporter genes were used to assess the expression of proteins, mRNA and the activity of the CaMKII/HDAC4/MEF2C signal pathway in vivo and in vitro. We found that Sta blocked cardiac hypertrophy induced by pressure overload. We also demonstrated that Sta inhibited nuclear export or promoted nuclear import of HDAC4 through regulation of p-CaMKII, and it further improved the repression of MEF2C. Taken together, our findings demonstrated that Sta ameliorates cardiac hypertrophy through CaMKII/HDAC4/MEF2C signal pathway.
盐酸水苏碱（Sta）是一种活性生物碱，从传统中药益母草中分离得到。在先前的研究中，我们实验室发现了Sta的心脏保护作用。然而，Sta的潜在机制尚未完全阐明。本研究的目的是详细阐述Sta对转录调控的抗肥厚作用。在体内，对C57BL/6J小鼠进行主动脉缩窄（TAC），并口服给予Sta。通过形态学评估、超声心动图参数、组织学分析和免疫荧光来评估心脏肥大。在体外，用去甲肾上腺素（PE）刺激心肌细胞，并通过免疫荧光和实时聚合酶链反应（RT-PCR）检测细胞表面和肥大标志物。此外，采用蛋白质印迹法、RT-PCR和荧光素酶报告基因来评估体内外蛋白质、mRNA的表达以及CaMKII/HDAC4/MEF2C信号通路的活性。我们发现Sta可阻断压力超负荷诱导的心脏肥大。我们还证明，Sta通过调节p-CaMKII抑制HDAC4的核输出或促进其核输入，并进一步增强对MEF2C的抑制作用。综上所述，我们的研究结果表明，Sta通过CaMKII/HDAC4/MEF信号通路改善心脏肥大。
