title: Thymoquinone attenuates monocrotaline-induced pulmonary artery hypertension via inhibiting pulmonary arterial remodeling in rats.
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.
  
  
  OBJECTIVE
  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.
authors.affiliation: Department of Cardiology, The Fifth Affiliated Hospital of Wenzhou Medical University, Lishui Central Hospital, Zhejiang 323000, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Zhu
authors.affiliation: Department of Cardiology, The Fifth Affiliated Hospital of Wenzhou Medical University, Lishui Central Hospital, Zhejiang 323000, China.
authors.forename: Xuyong
authors.initials: X
authors.lastname: Zhao
authors.affiliation: Department of Cardiology, The Fifth Affiliated Hospital of Wenzhou Medical University, Lishui Central Hospital, Zhejiang 323000, China.
authors.forename: Yijia
authors.initials: Y
authors.lastname: Xiang
authors.affiliation: Department of Cardiology, The Fifth Affiliated Hospital of Wenzhou Medical University, Lishui Central Hospital, Zhejiang 323000, China.
authors.forename: Shiyong
authors.initials: S
authors.lastname: Ye
authors.affiliation: Department of Cardiology, The Fifth Affiliated Hospital of Wenzhou Medical University, Lishui Central Hospital, Zhejiang 323000, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Huang
authors.affiliation: Department of Cardiology, The Fifth Affiliated Hospital of Wenzhou Medical University, Lishui Central Hospital, Zhejiang 323000, China.
authors.forename: Wuming
authors.initials: W
authors.lastname: Hu
authors.affiliation: Department of Cardiology, The Fifth Affiliated Hospital of Wenzhou Medical University, Lishui Central Hospital, Zhejiang 323000, China.
authors.forename: Linchun
authors.initials: L
authors.lastname: Lv
authors.affiliation: Department of Cardiology, The Fifth Affiliated Hospital of Wenzhou Medical University, Lishui Central Hospital, Zhejiang 323000, China. Electronic address: zengchunlai@medmail.com.cn.
authors.forename: Chunlai
authors.initials: C
authors.lastname: Zeng
mesh_terms: D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D016227:Benzoquinones / Q000494:pharmacology*; D004195:Disease Models, Animal; D006976:Hypertension, Pulmonary / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D017380:Hypertrophy, Right Ventricular / Q000473:pathology / Q000503:physiopathology; D016686:Monocrotaline / Q000494:pharmacology; D016328:NF-kappa B / Q000378:metabolism; D011651:Pulmonary Artery / Q000473:pathology / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects*; D016896:Treatment Outcome; D066253:Vascular Remodeling / Q000187:drug effects*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D000470:Alkaloids; D000970:Antineoplastic Agents; D016227:Benzoquinones; D016328:NF-kappa B; D016686:Monocrotaline; D048051:p38 Mitogen-Activated Protein Kinases; C003466:thymoquinone
keywords: Migration; Proliferation; Pulmonary arterial hypertension; Thymoquinone; p38MAPK/NF-κB