Thymoquinone attenuates monocrotaline-induced pulmonary artery hypertension via inhibiting pulmonary arterial remodeling in rats. (15th October 2016)

• Record Type: Journal Article
• Authors: Zhu, Ning; Zhao, Xuyong; Xiang, Yijia; Ye, Shiyong; Huang, Jie; Hu, Wuming; Lv, Linchun; Zeng, Chunlai
• Is Part Of: International journal of cardiology. Volume 221(2016)
• Page Start: 587
• Page End: 596
• Publication Date: 2016-10-15
• Subjects: Pulmonary arterial hypertension -- Thymoquinone -- Proliferation -- Migration -- p38MAPK/NF-κB; Cardiology -- Periodicals; Electronic journals; 616.12
• DOI: 10.1016/j.ijcard.2016.06.192
• Languages: English
• ISSNs: 0167-5273

Abstract

Abstract: Background: Pulmonary 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. Objectives: In the current study, we investigated effects of TQ on MCT-induced PAH in rats and its underlying mechanisms. Methods: After 2 weeks of monocrotaline injection (MCT, 60 mg/kg), Male Sprague–Dawley rats received TQ (8 mg/kg, 12 mg/kg, 16 mg/kg) or olive oil per day for 2 weeks. Hemodynamic changes, right ventricular hypertrophy, and lung morphological features were examined 4 weeks 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. Results: MCT-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. Conclusions: TQ ameliorates MCT-induced pulmonary artery hypertension by inhibiting pulmonary arterial remodeling partially via p38MAPK/NF-κB signaling pathway in rats. Highlights: TQ ameliorated MCT-induced PAH and pulmonary artery remodeling in rats. TQ induced apoptosis of PASMCs via elevating Bax/Bcl-2 ratio. TQ attenuated MCT-induced PAH through inhibition of activation of p38MAPK/NF-κB signaling pathway.