补阳还五汤改善低氧性肺动脉高压血管重塑中的作用及其机制研究

The Role and Mechanisms of Bu Yang Huan Wu Decoction in Improving Vascular Remodeling in Hypoxic Pulmonary Hypertension

摘要: 目的：探讨补阳还五汤在低氧性肺动脉高压(HPH)中的干预作用及其潜在机制，评估其对肺血管重塑、肺动脉压力、右心室肥厚、自噬与凋亡等方面的影响。方法：采用低氧诱导的HPH小鼠模型与原代肺动脉平滑肌细胞(PASMCs)模型，结合HE染色、右心导管法、右心室肥厚指数(RVHI)、TUNEL染色、Western blot、划痕实验与LC3免疫荧光等技术，系统评估补阳还五汤的干预效果。研究通过观察肺血管重塑、肺动脉压力、右心室功能、自噬与凋亡的分子机制，探讨其作用途径。结果：补阳还五汤显著改善低氧诱导的肺血管重塑，减少肺动脉压力和右心室肥厚，且具有剂量依赖性。低剂量组(BHD-L)和高剂量组(BHD-H)均能抑制PASMCs的异常迁移、减少细胞凋亡，并调节自噬通路，恢复自噬稳态。高剂量组的干预效果更加显著，提示其对HPH的治疗具有潜力。结论：补阳还五汤通过多途径调节PASMCs的代谢、自噬、凋亡与迁移行为，显著改善HPH的病理变化。该方剂为HPH的治疗提供了新的安全、经济且有效的治疗策略，并为中医药在肺血管疾病中的现代化应用提供了科学依据。

Abstract: Objective: This paper aims to investigate the effects and mechanisms of Bu Yang Huan Wu Decoction in hypoxic pulmonary hypertension (HPH), focusing on pulmonary vascular remodeling, pulmonary arterial pressure, right ventricular hypertrophy, autophagy, and apoptosis. Methods: Hypoxia-induced HPH mouse and PASMC models were established. HE staining, right heart catheterization, RVHI, TUNEL, Western blot, scratch assay, and LC3 immunofluorescence were used to assess the effects of Bu Yang Huan Wu Decoction and explore related mechanisms. Results: Bu Yang Huan Wu Decoction significantly alleviated pulmonary vascular remodeling, reduced pulmonary arterial pressure and right ventricular hypertrophy, and showed dose-dependent effects. Both the low-dose group (BHD-L) and the high-dose group (BHD-H) can inhibit the abnormal migration of pulmonary artery smooth muscle cells (PASMCs), reduce cell apoptosis, regulate the autophagy pathway, and restore autophagy homeostasis. The intervention effect of the high-dose group is more significant, suggesting its potential for the treatment of hypoxic pulmonary hypertension (HPH). Conclusion: Bu Yang Huan Wu Decoction improves HPH pathological changes by regulating PASMC autophagy, apoptosis, metabolism, and migration. This prescription offers a novel, safe, cost-effective, and efficient treatment strategy for HPH, and provides a scientific basis for the modern application of traditional Chinese medicine in pulmonary vascular diseases.