Zhang Xiaozheng, Chen Jun, Xu Pan, Tian Xin
Department of Cardiology , Traditional Chinese Medicine Hospital of Shaanxi Province , Xi'an , Shaanxi Province , China . Email:
Department of Encephalopathy , Traditional Chinese Medicine Hospital of Shaanxi Province , Xi'an , Shaanxi Province , China.
Medchemcomm. 2018 Sep 4;9(10):1715-1721. doi: 10.1039/c8md00341f. eCollection 2018 Oct 1.
The present study aimed to evaluate the protective effects of astragaloside IV (As-IV) against hypoxic pulmonary hypertension (HPH) and its mechanisms of action. Sprague-Dawley rats were used in a model of HPH induced by chronic hypoxia. After hypoxia, the mean pulmonary arterial pressure (mPAP), right ventricular pressure (RVP), and right ventricular hypertrophy index (RVHI) were monitored. Relaxation of the pulmonary artery in response to As-IV was measured. The levels of endothelin-1 (ET-1), angiotensin II (Ang II), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) in serum were assessed. Cell proliferation was detected by the cell counting kit-8 (CCK-8) assay. Treatment with As-IV significantly decreased mPAP, RVP and RV/(LV + S) and attenuated the development of HPH. Moreover, As-IV time-dependently relaxed the pulmonary arteries from HPH rats. In addition, As-IV decreased the levels of ET-1, Ang II, TNF-α, and IL-6 in serum of HPH rats. experiments demonstrated that As-IV also significantly inhibited the proliferation of pulmonary artery smooth muscle cells (PASMCs) subjected to hypoxia. Our findings suggested the therapeutic potential of As-IV in the treatment of pulmonary hypertension.
本研究旨在评估黄芪甲苷IV(As-IV)对缺氧性肺动脉高压(HPH)的保护作用及其作用机制。采用Sprague-Dawley大鼠建立慢性缺氧诱导的HPH模型。缺氧后,监测平均肺动脉压(mPAP)、右心室压力(RVP)和右心室肥厚指数(RVHI)。测定As-IV对肺动脉的舒张作用。评估血清中内皮素-1(ET-1)、血管紧张素II(Ang II)、肿瘤坏死因子-α(TNF-α)和白细胞介素-6(IL-6)的水平。采用细胞计数试剂盒-8(CCK-8)法检测细胞增殖。As-IV治疗显著降低了mPAP、RVP和RV/(LV + S),并减轻了HPH的发展。此外,As-IV对HPH大鼠的肺动脉具有时间依赖性的舒张作用。此外,As-IV降低了HPH大鼠血清中ET-1、Ang II、TNF-α和IL-6的水平。实验表明,As-IV还显著抑制了缺氧条件下肺动脉平滑肌细胞(PASMCs)的增殖。我们的研究结果提示As-IV在治疗肺动脉高压方面具有潜在的治疗价值。