Abstract
Pulmonary arterial hypertension (PAH) is associated with increased inflammation and abnormal vascular remodeling. Astragaloside IV (ASIV), a purified small molecular saponin contained in the well‑know herb, Astragalus membranaceus, is known to exert anti‑inflammatory and anti‑proliferation effects. Thus, the present study investigated the possible therapeutic effects of ASIV on monocrotaline (MCT)‑induced PAH. Rats were administered a single intraperitoneal injection of MCT (60 mg/kg), followed by treatment with ASIV at doses of 10 and 30 mg/kg once daily for 21 days. Subsequently, right ventricle systolic pressure, right ventricular hypertrophy and serum inflammatory cytokines, as well as pathological changes of the pulmonary arteries, were examined. The effects of ASIV on the hypoxia‑induced proliferation and apoptotic resistance of human pulmonary artery smooth muscle cells (HPASMCs) and the dysfunction of human pulmonary artery endothelial cells (HPAECs) were evaluated. MCT elevated pulmonary artery pressure and promoted pulmonary artery structural remodeling and right ventricular hypertrophy in the rats, which were all attenuated by both doses of ASIV used. Additionally, ASIV prevented the increase in the TNF‑α and IL‑1β concentrations in serum, as well as their gene expression in lung tissues induced by MCT. In in vitro experiments, ASIV attenuated the hypoxia‑induced proliferation and apoptotic resistance of HPASMCs. In addition, ASIV upregulated the protein expression of p27, p21, Bax, caspase‑9 and caspase‑3, whereas it downregulated HIF‑1α, phospho‑ERK and Bcl‑2 protein expression in HPASMCs. Furthermore, in HPAECs, ASIV normalized the increased release of inflammatory cytokines and the increased protein levels of HIF‑1α and VEGF induced by hypoxia. On the whole, these results indicate that ASIV attenuates MCT‑induced PAH by improving inflammation, pulmonary artery endothelial cell dysfunction, pulmonary artery smooth muscle cell proliferation and resistance to apoptosis.