Ning Zhu1, Xuyong Zhao1, Yijia Xiang1, Shiyong Ye1, Jie Huang1, Wuming Hu1, Linchun Lv1, Chunlai Zeng2. 1. Department of Cardiology, The Fifth Affiliated Hospital of Wenzhou Medical University, Lishui Central Hospital, Zhejiang 323000, China. 2. Department of Cardiology, The Fifth Affiliated Hospital of Wenzhou Medical University, Lishui Central Hospital, Zhejiang 323000, China. Electronic address: zengchunlai@medmail.com.cn.
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 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. 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.
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 humannonsmall-cell lung cancer cells and humanglioblastoma cells. OBJECTIVES: In the current study, we investigated effects of TQ on MCT-induced PAH in rats and its underlying mechanisms. METHODS: After 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. 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.