The aim of the present study was to investigate the impact of N‑acetylcysteine (NAC) on the expression of reduced nicotinamide adenine dinucleotide phosphate oxidase 1 (Nox1), and the proliferation and apoptosis of pulmonary artery smooth muscle cells (PASMCs) in rats exhibiting monocrotaline (MCT)‑induced pulmonary hypertension, and to investigate the possible mechanisms and treatment roles of NAC in pulmonary vascular remodeling (PVR). A total of 18 Wistar rats were randomly divided into three groups: The control (C) group; the MCT (M) group; and the NAC (N) group. The right ventricular hypertrophy index (RVHI) and other indicators were recorded 6 weeks subsequently. Groups C and M were divided into two subgroups: Groups C1 and M1 (control); and group C2 and M2 group (treated with ML171). Group N was not sub‑divided. PASMCs were isolated, and the vascular remodeling and Nox1 positioning were observed. The expression of Nox mRNA in each group, and the proliferation, apoptosis, and superoxide dismutase (SOD) activity of PASMCs, prior to and following the ML171 treatment, were measured. NAC was able to decrease RVHI and other indicators (P<0.001). The mRNA expression of Nox1 and Nox4 in group M was significantly increased compared with group C (P<0.05), and NAC was able to significantly decrease the expression of these two factors in lung tissue (P<0.001). MCT‑PASMCs exhibited differences in Nox1 mRNA expression (P<0.001), and the total SOD activity was Nox1‑dependently increased (r=0.949; P<0.001). NAC was able to decrease Nox1‑derived reactive oxygen species in PASMCs, thereby improving PVR. Nox1 was able to increase SOD activity, thereby demonstrating its positive effect on the proliferation of MCT‑PASMCs.
The aim of the present study was to investigate the impact of N-acetylcysteine (NAC) on the expression of activin receptor-like kinase-1 (ALK-1) and mothers against decapentaplegic homolog 1 (Smad1) in the pulmonary artery of rats with pulmonary arterial hypertension (PAH), and to explore the possible mechanisms underlying its effects on pulmonary vascular remodeling (PVR). In total, 32 Wistar rats were randomly divided into four groups: Control, model, low-dose (100 mg/kg/day) NAC and high-dose (500 mg/kg/day) NAC. Monocrotaline (MCT) was intraperitoneally injected to prepare the model, and the right ventricular hypertrophy index (RVHI) and hemodynamic parameters were detected 6 weeks later. Hematoxylin and eosin staining was used to observe the pulmonary arterial structural changes and evaluate the peri-pulmonary artery inflammation score. Additionally, western blot analysis was used to detect the protein expression of ALK-1 and Smad1 in the pulmonary artery. The results demonstrated that treatment with NAC reduced RVHI and mean pulmonary artery pressure. In addition, NAC reduced the MCT-induced PVR, pulmonary inflammation score and upregulation of ALK-1 and Smad1. These results indicate that ALK-1 and Smad1 participate in the formation of PAH and the process of PVR, and suggest that NAC may inhibit PAH by inhibiting the expression of ALK-1 and Smad1 in the pulmonary artery.
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