• Ning Zhu, Xuyong Zhao, Yijia Xiang, Shiyong Ye, Jie Huang, Wuming Hu, Linchun Lv, and Chunlai Zeng.
• Department of Cardiology, The Fifth Affiliated Hospital of Wenzhou Medical University, Lishui Central Hospital, Zhejiang 323000, China.
• Int. J. Cardiol. 2016 Oct 15; 221: 587-96.

BackgroundPulmonary artery remodeling induced by excess proliferation, migration and apoptosis resistance of pulmonary arterial smooth muscle cells (PASMCs) is a key component in pulmonary artery hypertension (PAH). Thymoquinone (TQ) triggers cancer cells apoptosis through multiple mechanisms. In addition, TQ inhibits migration of human nonsmall-cell lung cancer cells and human glioblastoma cells.ObjectivesIn the current study, we investigated effects of TQ on MCT-induced PAH in rats and its underlying mechanisms.MethodsAfter 2weeks of monocrotaline injection (MCT, 60mg/kg), Male Sprague-Dawley rats received TQ (8mg/kg, 12mg/kg, 16mg/kg) or olive oil per day for 2weeks. Hemodynamic changes, right ventricular hypertrophy, and lung morphological features were examined 4weeks later. In addition, TUNEL, PCNA, α-SMA, Bax and Bcl-2 were detected by immunohistochemistry staining. Bax, Bcl-2, cleaved caspase-3, cleaved poly (ADP-ribose) polymerase (PARP) MMP2, MMP9 and activation of p38MAPK and NF-κB were assessed by Western blot.ResultsMCT-induced an increase in pulmonary blood pressure and right ventricular hypertrophy, which were attenuated by TQ treatment. TQ also blocked MCT-induced pulmonary arterial remodeling, proliferation of PASMCs, elevation of MMP2 and downregulation of ratio of Bax/Bcl-2, cleaved caspase-3 and cleaved PARP. Furthermore, TQ inhibited MCT-induced activation of p38MAPK and NF-κB.ConclusionsTQ ameliorates MCT-induced pulmonary artery hypertension by inhibiting pulmonary arterial remodeling partially via p38MAPK/NF-κB signaling pathway in rats.Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

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