Astragalus polysaccharide protects mice against pulmonary vascular remodeling after hypoxia-induced pulmonary hypertension

Abstract

Objective To investigate the effects of astragalus polysaccharide (APS) on pulmonary vascular remodeling in mice with hypoxic pulmonary hypertension (HPH) and explore its related mechanism. Methods Fifty male C57BL/6 mice were randomly and equally divided into normal control group, model group, and model+APS (200, 400 and 800 mg/kg) groups. The mice in the model and model+APS groups were kept in a normal pressure hypoxia chamber containing 10% O2 for 4 weeks to prepare a pulmonary hypertension model. In 4 weeks later, right ventricular systolic pressure (RVSP) and right heart hypertrophy index RV/(LV+S) were measured. HE staining and Masson staining were used to observe the pathological changes and the collagen deposition in the pulmonary arterioles, respectively. Immunofluorescence assay was adopted to detect the protein level of α-SMA in the pulmonary arterioles. The contents of serum C-reactive protein (CRP), IL-6 and TNF-α were determined by ELISA, and the protein levels of Krüppel-like factor 5 (KLF5), hypoxia-inducible factor 1α (HIF-1α), Cyclin B1, Cyclin D1, VEGF and TGF-β1 in lung tissues were tested by Western blotting. Results As compared with the normal control group, the RVSP and RV/(LV+S) were significantly increased, the pulmonary arteriole wall was thickened, and the area of collagen deposition was enlarged in the model group. In addition, the contents of CRP, IL-6, TNF-α, and the protein levels of α-SMA, KLF5, HIF-1α, Cyclin B1, Cyclin D1, VEGF and TGF-β1 were all notably elevated in the model group (P < 0.01). In comparison with the model group, the RVSP, RV/(LV+S) and pathological changes of pulmonary arterioles were alleviated, the collagen deposition area was remarkably reduced, and the levels of CRP, IL-6, TNF-α, α-SMA, KLF5, HIF-1α, Cyclin B1, Cyclin D1, VEGF, TGF-β1 were greatly decreased in the APS treatment groups (P < 0.01). Conclusion APS shows a protective effect on pulmonary vascular remodeling in mice with hypoxia-induced pulmonary hypertension, which may be related to its inhibition on KLF5/HIF-1α signaling pathway.

Keywords

• astragalus polysaccharide
• hypoxic pulmonary hypertension
• klf5/hif-1α signaling pathway
• vascular remodeling