缺氧(环境)
体内
药理学
肺动脉高压
医学
心室
右心室肥大
炎症
心室压
心脏病学
化学
内科学
血流动力学
生物
生物技术
有机化学
氧气
作者
Congke Zhao,Linlin Hu,Xinkuai He,Lijun Li,Minghui Yin,Abraham Terkpertey Tettey,Yu Wang,Jingshan Shen,Siyuan Tang,Chunhui Wu,Qianbin Li,Zhen Wang,Xiaohui Li
标识
DOI:10.1016/j.vph.2022.107017
摘要
Pulmonary hypertension (PH) is a progressive and life-threatening disease with poor prognosis despite many advances in medical therapy over the past 20 years. Novel therapies which target on the underlying pathology of PH are still urgent to be met. TPN171H is a recently found new compound that exhibits potent pharmacological effects in PH via inhibiting phosphodiesterase type 5 (PDE-5). However, as one icariin derivative, the anti-inflammatory effects of TPN171H for treating PH are not clear. The present study was designed to investigate the therapeutical effect of TPN171H against inflammation in PH and reveal the underlying mechanism. Hypoxia and monocrotaline (MCT)-induced PH rat models were established, which were treated by oral administration of TPN171H (5, 25 mg/kg/d) or sildenafil (25 mg/kg/d). The right ventricle systolic pressure (RVSP), right ventricle hypertrophy index (RVHI) and vascular remodeling were measured. The results suggested that TPN171H significantly reduced RVSP and RVHI, and reversed pulmonary vascular remodeling in rats with both models. Furthermore, in in vivo and in vitro research, our data suggested that TPN171H remarkably suppressed cathepsin B-mediated NLRP3 inflammasome activation, which may contribute to its therapeutical function for PH.
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