Department of Traditional Chinese Medicine (Institute of Integration of Traditional and Western Medicine of Guangzhou Medical University, State Key Laboratory of Respiratory Disease), The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, 510260, China.
Guangzhou Institute of Cardiovascular Disease, Guangdong Key Laboratory of Vascular Diseases, State Key Laboratory of Respiratory Disease, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510260, China.
J Ethnopharmacol. 2021 Apr 24;270:113838. doi: 10.1016/j.jep.2021.113838. Epub 2021 Jan 16.
Myocardial fibrosis after myocardial infarction (MI) leads to cardiac remodeling and loss of function. Taohong siwu decoction (THSWD), a well-known traditional Chinese medicinal prescription, has been clinically used to treat various cardiovascular and cerebrovascular diseases, but its potential functions in myocardial fibrosis after MI remain uncharacterized.
The purpose of current study was to explore the potential mechanism action and anti-myocardial fibrosis effects of treatment with THSWD in vivo and in vitro.
Mouse underwent ligation of coronary artery to induce MI and divided equally into the sham group, model group and THSWD treatment groups. After 4 weeks, the effects of THSWD treatment on cardiac function were estimated by echocardiography. HE staining was used to detect the pathologic changes and Masson trichrome staining was used to estimate tissue fibrosis. To further explore the regulatory molecular mechanisms of THSWD, transcriptome analysis was performed. Furthermore, in vitro, we investigated the effect of THSWD on cell proliferation and collagen deposition in primary cardiac fibrosis cells and its possible mechanism of action. Overexpression of TGFBR1 was achieved by infection with an adenovirus vector encoding TGFBR1.
Treatment with THSWD significantly decreased myocardial fibrosis and recovered cardiac function in the post-MI mouse. The transcriptomics data imply that the TGF-β pathway might be a target in the anti-fibrosis effect of THSWD. THSWD inhibits TGF-β1-induced proliferation of primary cardiac fibroblasts. THSWD decreased collagen expression and TGFBR1 and Smad2/3 phosphorylation. Moreover, the inhibitory effect of THSWD on CFs proliferation and collagen deposition, as well as TGFBR1 signaling pathway-associated proteins expression was partially abrogated by overexpression of TGFBR1.
Collectively, the results implicate that THSWD attenuates myocardial fibrosis by inhibiting fibrosis proliferation and collagen deposition via inhibiting TGFBR1, and might be a potential therapeutic agent for treatment of myocardial fibrosis post-MI.
心肌梗死后心肌纤维化导致心脏重构和功能丧失。桃红四物汤（THSWD）是一种著名的中药方剂，已临床用于治疗各种心脑血管疾病，但它在心肌梗死后心肌纤维化中的潜在作用尚未确定。
本研究旨在探讨 THSWD 体内和体外抗心肌纤维化的潜在作用机制。
小鼠进行冠状动脉结扎诱导心肌梗死，并平均分为假手术组、模型组和 THSWD 治疗组。4 周后，通过超声心动图评估 THSWD 治疗对心脏功能的影响。HE 染色用于检测病理变化，Masson 三色染色用于评估组织纤维化。为了进一步探讨 THSWD 的调节分子机制，进行了转录组分析。此外，在体外，我们研究了 THSWD 对原代心肌纤维化细胞增殖和胶原沉积的影响及其可能的作用机制。通过感染携带 TGFBR1 的腺病毒载体实现 TGFBR1 的过表达。
THSWD 治疗显著减少心肌纤维化并恢复心肌梗死后小鼠的心脏功能。转录组学数据表明，TGF-β 通路可能是 THSWD 抗纤维化作用的靶点。THSWD 抑制 TGF-β1 诱导的原代心肌成纤维细胞增殖。THSWD 降低胶原表达和 TGFBR1 及 Smad2/3 磷酸化。此外，通过过表达 TGFBR1，THSWD 对 CFs 增殖和胶原沉积以及 TGFBR1 信号通路相关蛋白表达的抑制作用部分被阻断。
总之，这些结果表明，THSWD 通过抑制 TGFBR1 抑制纤维化增殖和胶原沉积来减轻心肌纤维化，可能是治疗心肌梗死后心肌纤维化的潜在治疗剂。
