Pulmonary arterial hypertension (PAH) is closely associated with profound vascular remodeling, especially pulmonary arterial medial hypertrophy and muscularization, due to aberrant proliferation of pulmonary artery smooth muscle cells (PASMCs). Berberine, a drug commonly used to treat inflammation, may be a novel therapeutic option for PAH by improving pulmonary artery remodeling. The present study investigated whether berberine affected Trx1/β-catenin expression and/or activity and whether it could reduce the development of pulmonary hypertension in an experimental rat model and proliferation in human PASMCs (HPASMCs). The results showed that increased proliferation in hypoxia-induced healthy PASMCs or PAH PASMCs was associated with a significant increase in Trx1 and β-catenin expression. Treatment with the Trx1-specific inhibitor PX-12 significantly reduced pulmonary arterial pressure and vascular remodeling, as well as improved in vivo cardiac function and right ventricular hypertrophy, in Su/Hox-induced PAH rats. Berberine reversed right ventricular systolic pressure and right ventricular hypertrophy and decreased pulmonary vascular remodeling in the rats. Furthermore, berberine had an antiproliferative effect on hypoxia-induced HPASMC proliferation in a manner likely mediated by inhibiting Trx1 and its target gene β-catenin expression. Our work will help elucidate novel strategies for PAH treatment involving the traditional Chinese medicine berberine, and Trx1/β-catenin may be a promising therapeutic target.

由于肺动脉平滑肌细胞（PASMC）的异常增殖，肺动脉高压（PAH）与深刻的血管重构密切相关，尤其是肺动脉内侧肥大和肌肉发达。小ber碱是一种常用于治疗炎症的药物，它可以通过改善肺动脉重塑成为PAH的新型治疗选择。本研究调查了小ber碱是否会影响Trx1 /β-catenin的表达和/或活性，以及​​能否降低实验性大鼠模型中肺动脉高压的发展和人类PASMCs（HPASMCs）的增殖。结果表明，低氧诱导的健康PASMCs或PAH PASMCs的增殖增加与Trx1和β-catenin表达的显着增加有关。在Su / Hox诱导的PAH大鼠中，用Trx1特异性抑制剂PX-12治疗可显着降低肺动脉压和血管重塑，并改善体内心脏功能和右心室肥大。小碱可逆转大鼠右室收缩压和右室肥大，并减少肺血管重构。此外，小ber碱可能通过抑制Trx1及其靶基因β-catenin的表达来介导低氧诱导的HPASMC增殖的抗增殖作用。我们的工作将有助于阐明涉及中药小ber碱的PAH治疗新策略，Trx1 /β-catenin可能是有希望的治疗靶点。Su / Hox诱导的PAH大鼠体内心脏功能改善和右心室肥大。小碱可逆转大鼠右室收缩压和右室肥大，并减少肺血管重构。此外，小ber碱可能通过抑制Trx1及其靶基因β-catenin的表达来介导低氧诱导的HPASMC增殖的抗增殖作用。我们的工作将有助于阐明涉及中药小ber碱的PAH治疗新策略，Trx1 /β-catenin可能是有希望的治疗靶点。Su / Hox诱导的PAH大鼠体内心脏功能改善和右心室肥大。小碱可逆转大鼠右室收缩压和右室肥大，并降低肺血管重构。此外，小ber碱可能通过抑制Trx1及其靶基因β-catenin的表达来介导低氧诱导的HPASMC增殖的抗增殖作用。我们的工作将有助于阐明涉及中药小ber碱的PAH治疗新策略，Trx1 /β-catenin可能是有希望的治疗靶点。小ber碱对缺氧诱导的HPASMC增殖具有抑制作用，其抑制作用可能是通过抑制Trx1及其靶基因β-catenin的表达介导的。我们的工作将有助于阐明涉及中药小ber碱的PAH治疗新策略，Trx1 /β-catenin可能是有希望的治疗靶点。小ber碱对缺氧诱导的HPASMC增殖具有抗增殖作用，其抑制作用可能是通过抑制Trx1及其靶基因β-catenin的表达介导的。我们的工作将有助于阐明涉及中药小ber碱的PAH治疗新策略，Trx1 /β-catenin可能是有希望的治疗靶点。