Institute of Basic Theory, China Academy of Chinese Medical Sciences, Beijing, 100700, China.
Basic Medical College, Hebei North University, Zhangjiakou, 075000, Hebei, China.
BMC Complement Altern Med. 2018 Sep 3;18(1):245. doi: 10.1186/s12906-018-2311-9.
Er-Xian decoction (EXD), a formula of Chinese medicine, is often used to treat menopausal syndrome in China. The aim of the present study was to explore the potential cardioprotective mechanism of EXD against myocardial injury in an ovariectomy-induced menopausal rat model.
We divided the female Wistar rats into ovariectomy group and sham operation group (SHAM group). The ovariectomized (OVX) rats received treatment of vehicle (OVX group), EXD (EXD group) or 17β-estradiol (E2 group). After 12-week of treatment, the level of estradiol in serum was detected using an electrochemiluminescence immunoassay, and electrophysiologic changes in myocardial action potentials (AP) were evaluated using intracellular microelectrode technique. Changes in the histopathology of the left ventricle and the ultrastructure of the cardiomyocytes were observed by hematoxylin and eosin (HE) staining and transmission electronmicroscopy to assess myocardial injury. Microarrays were applied for the evaluation of gene expression profiles in ventricular muscle of the OVX and EXD rats. Further pathway analyses of the differential expression genes were carried out using the Kyoto Encyclopedia of Genes and Genomes (KEGG). And real-time quantitative RT-PCR (qRT-PCR) was used for verification of the key findings.
The results from electrophysiological and histomorphological observations demonstrated that EXD had a substantial myocardial protective effect. The EXD-treated rats, in comparison with the OVX rats, demonstrated up-regulated expression of 28 genes yet down-regulated expression of 157 genes in the ventricular muscle. The qRT-PCR assay validated all selected differential expression genes. The KEGG pathway analysis showed that the down-regulated genes were relevant to cardiomyopathy and myocardial contractility. EXD could decrease the mRNA expressions of cardiac myosin (Myh7, Myl2) and integrin (Itgb5) in the ventricular myocardium.
EXD had a protective effect against myocardial injury in OVX rats, and this cardioprotective effect may be associated with modulation of the expression of cardiac myosin or integrin at the mRNA level.
二仙汤（EXD）是一种中药方剂，常用于治疗中国女性的更年期综合征。本研究旨在探讨 EXD 对去卵巢诱导的更年期大鼠模型心肌损伤的潜在心脏保护作用。
将雌性 Wistar 大鼠分为去卵巢组和假手术组（SHAM 组）。去卵巢（OVX）大鼠给予 vehicle（OVX 组）、EXD（EXD 组）或 17β-雌二醇（E2 组）治疗。治疗 12 周后，采用电化学发光免疫分析法检测血清中雌二醇水平，采用细胞内微电极技术评估心肌动作电位（AP）的电生理变化。采用苏木精-伊红（HE）染色和透射电镜观察左心室组织病理学和心肌细胞超微结构变化，评估心肌损伤。应用微阵列评估 OVX 和 EXD 大鼠心室肌的基因表达谱。采用京都基因与基因组百科全书（KEGG）对差异表达基因进行通路分析，并采用实时定量 RT-PCR（qRT-PCR）验证关键发现。
电生理和组织形态学观察结果表明，EXD 具有显著的心肌保护作用。与 OVX 大鼠相比，EXD 治疗组大鼠心室肌中 28 个基因上调，157 个基因下调。qRT-PCR 检测验证了所有选定的差异表达基因。KEGG 通路分析显示，下调基因与心肌病和心肌收缩力相关。EXD 可降低心室心肌中肌球蛋白（Myh7、Myl2）和整合素（Itgb5）的 mRNA 表达。
EXD 对 OVX 大鼠心肌损伤具有保护作用，这种心脏保护作用可能与调节心肌球蛋白或整合素的 mRNA 表达有关。
