Abstract: Objective　To explore the inhibitory effect of astragaloside (AST) on the pathological development of hypoxic pulmonary hypertension (HPH) and its relevant mechanism. Methods　Twenty-eight SPF male Sprague-Dawley rats were randomly divided into 4 groups (7 rats per group): control group, HPH group, HPH+AST15 [15 mg/(kg·d)] group, and HPH+AST45 [45 mg/(kg·d)] group. The rat model of HPH was established by intermittent normal pressure hypoxia. After 28-day hypoxia exposure, the right ventricle systolic pressure (RVSP) and the weight ratio of RV/(LV+S) were recorded. After HE and immunofluorescence staining, the percent medial wall thickness (WT), percent medial wall area (WA), and integrated optical density (OD) value of α-smooth muscle actin (α-SMA) in pulmonary arteries were determined to investigate pulmonary artery structural remodeling. The content of SOD, CAT and MDA both in serum and in lung tissues were measured by spectrophotometry. The NADPH (reduced nicotinamide adenine dinucleotide phosphate) oxidase Nox2 and Nox4 protein expressions in lung tissues were detected by Western blot analysis. Results　 Compared with those in control group, the RVSP, RV/(LV+S) ratio, WT, WA, and α-SMA value were increased significantly in HPH group (P＜0.05), SOD and CAT levels both in serum and in lung tissues were decreased significantly in association with the elevated MDA content (P＜0.05), and the Nox2 and Nox4 protein levels in lung tissues were increased significantly (P＜0.05). However, compared with HPH group, the RVSP, RV/(LV+S) ratio, WT, WA, and α-SMA value were decreased significantly (P＜0.05), SOD and CAT levels both in serum and in lung tissues were increased significantly in association with the decreased MDA content (P＜0.05), and the Nox2 and Nox4 protein levels in lung tissues were significantly decreased (P＜0.05) in HPH+AST15 group and HPH+AST45 group. In addition, the WT, WA, α-SMA value, MDA level in lung tissues, and Nox2 and Nox4 protein levels in lung tissues were significantly decreased in HPH+AST45 group than those of the HPH+AST15 group (P＜0.05). Conclusion　AST can attenuate the pathological development of HPH in rats, which may be associated with the elevating levels of SOD and CAT and inhibiting the expressions of Nox2 and Nox4 in rats.

Key words: hypertension, pulmonary, hypoxia, reactive oxygen species, disease models, animal, NADPH oxidase, astragalus total saponins, oxidative stress, antioxidant enzyme