Zeng Zuomei, Wang Xinyue, Wang Hongjuan, Tian Leiyu, Cui Lidan, Guo Jian, Chen Yucai
School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China.
School of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing 100029, China.
Vascul Pharmacol. 2025 Mar;158:107467. doi: 10.1016/j.vph.2025.107467. Epub 2025 Jan 31.
Pulmonary hypertension (PH) is a serious vascular disease characterized by pulmonary vascular remodeling. Xuefu Zhuyu decoction (XFZYD) can potentially improve pulmonary vascular remodeling; however, its mechanism requires further investigation.
Rat models of monocrotaline (MCT)-induced PH and chronic thromboembolic pulmonary hypertension (CTEPH) were employed to investigate whether XFZYD has the potential to improve pulmonary vascular remodeling. After 21 days of XFZYD administration, the right ventricular systolic pressure (RVSP), organ indices, and wall thickness of pulmonary arteries of the rats were measured. Considering the possibility of endothelial-to-mesenchymal transition (EndMT), the specific mechanism of XFZYD in improving pulmonary vascular remodeling was further explored. Immunofluorescence, immunohistochemistry, and western blotting were used to detect the expression of EndMT markers, transforming growth factor-β1 (TGF-β1)/Smad pathway-related proteins, hypoxia-inducible factor-1α (HIF-1α), and levels of reactive oxygen species (ROS) in the lung tissues.
XFZYD demonstrated significant efficacy in treating PH, as evidenced by its effects in both the rat models of MCT-induced PH and CTEPH. XFZYD remarkably improved pulmonary vascular remodeling while reducing RVSP and right ventricular hypertrophy. XFZYD has the potential to improve pulmonary vascular remodeling by inhibiting EndMT in the pulmonary vasculature. The underlying mechanism may be closely associated with the inhibition of TGF-β1/Smad and HIF-1α signaling pathways and the reduction of ROS levels in lung tissue by XFZYD.
This study indicates that XFZYD may inhibit EndMT by modulating the ROS/HIF-1α/TGF-β1 signaling pathway, thereby improving pulmonary vascular remodeling. These findings provide a theoretical foundation for the clinical application of XFZYD in PH.
肺动脉高压（PH）是一种以肺血管重塑为特征的严重血管疾病。血府逐瘀汤（XFZYD）可能改善肺血管重塑；然而，其机制需要进一步研究。
采用野百合碱（MCT）诱导的PH大鼠模型和慢性血栓栓塞性肺动脉高压（CTEPH）大鼠模型，研究XFZYD是否具有改善肺血管重塑的潜力。给予XFZYD 21天后，测量大鼠的右心室收缩压（RVSP）、器官指数和肺动脉壁厚度。考虑到内皮-间充质转化（EndMT）的可能性，进一步探讨XFZYD改善肺血管重塑的具体机制。采用免疫荧光、免疫组织化学和蛋白质免疫印迹法检测肺组织中EndMT标志物、转化生长因子-β1（TGF-β1）/Smad通路相关蛋白、缺氧诱导因子-1α（HIF-1α）的表达以及活性氧（ROS）水平。
XFZYD在治疗PH方面显示出显著疗效，在MCT诱导的PH大鼠模型和CTEPH大鼠模型中均有体现。XFZYD显著改善肺血管重塑，同时降低RVSP和右心室肥厚。XFZYD有可能通过抑制肺血管中的EndMT来改善肺血管重塑。其潜在机制可能与XFZYD抑制TGF-β1/Smad和HIF-1α信号通路以及降低肺组织中ROS水平密切相关。
本研究表明，XFZYD可能通过调节ROS/HIF-1α/TGF-β1信号通路抑制EndMT，从而改善肺血管重塑。这些发现为XFZYD在PH临床应用中提供了理论基础。
