Interventions and mechanisms of N‑acetylcysteine on monocrotaline‑induced pulmonary arterial hypertension

Yu,Wencheng; Song,Xiaoxia; Lin,Chen; Ji,Weina

doi:10.3892/etm.2018.6103

Interventions and mechanisms of N‑acetylcysteine on monocrotaline‑induced pulmonary arterial hypertension

Authors:
- Wencheng Yu
- Xiaoxia Song
- Chen Lin
- Weina Ji
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Affiliations: Department of Respiratory Medicine, Affiliated Hospital of Qingdao University, Qingdao, Shandong 266003, P.R. China, Department of Respiratory Medicine, Central Hospital of Shengli Oil Field, Dongying, Shandong 257000, P.R. China
Published online on: April 27, 2018 https://doi.org/10.3892/etm.2018.6103
Pages: 5503-5509

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Abstract

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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