4-Chloro-DL-phenylalanine protects against monocrotaline-induced pulmonary vascular remodeling and lung inflammation

Autor: Xin-Hua Zhang, Huai-Liang Wang, Ming Liu, Yang Bai, Jian Kang, Han-Ming Wang, Guo-Chao Lian, Yun Wang
Rok vydání: 2013
Předmět:
Male
medicine.medical_specialty
Pathology
Hypertension
Pulmonary
Phenylalanine
Interleukin-1beta
Down-Regulation
Inflammation
Tryptophan Hydroxylase
Biology
Matrix metalloproteinase
Proinflammatory cytokine
Rats
Sprague-Dawley
Western blot
Right ventricular hypertrophy
Internal medicine
Genetics
medicine
Animals
Familial Primary Pulmonary Hypertension
Lung
Tissue Inhibitor of Metalloproteinase-2
Monocrotaline
Tissue Inhibitor of Metalloproteinase-1
medicine.diagnostic_test
Tumor Necrosis Factor-alpha
Fenclonine
RNA-Binding Proteins
Pneumonia
General Medicine
Tissue inhibitor of metalloproteinase
Intercellular Adhesion Molecule-1
medicine.disease
Rats
Disease Models
Animal
Endocrinology
medicine.anatomical_structure
Matrix Metalloproteinase 9
Matrix Metalloproteinase 2
Tumor necrosis factor alpha
medicine.symptom
Zdroj: International Journal of Molecular Medicine. 33:373-382
ISSN: 1791-244X
1107-3756
DOI: 10.3892/ijmm.2013.1591
Popis: The present study was performed to investigate the effects of 4-chloro-DL-phenylalanine (PCPA), a tryptophan hydroxylase (Tph) inhibitor (TphI), on pulmonary vascular remodeling and lung inflammation in monocrotaline (MCT)-induced pulmonary arterial hypertension (PAH) in rats. Animal models of PAH were established using Sprague-Dawley (SD) rats by a single intraperitoneal injection of MCT (60 mg/kg). PCPA (50 or 100 mg/kg/day) was administered to the rats with PAH. On day 22, hemodynamic measurements and morphological observations of the lung tissues were performed. The levels of Tph-1 and serotonin transporter (SERT) in the lungs were analyzed by immunohistochemistry and western blot analysis. The expression of matrix metalloproteinase (MMP)-2 and MMP-9, tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2 and inflammatory cytokines were assayed by western blot analysis. The activity of MMP-2 and MMP-9 was evaluated by gelatin zymography (GZ). MCT markedly promoted PAH, increased the right ventricular hypertrophy index, pulmonary vascular remodeling, lung inflammation and mortality, which was associated with the increased expression of Tph-1, SERT, MMP-2/-9, TIMP-1/-2 and inflammatory cytokines. PCPA markedly attenuated MCT-induced pulmonary vascular remodeling and lung inflammation, inhibited the expression of Tph-1 and SERT and suppressed the expression of MMP-2/-9, TIMP-1/-2, interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α) and intercellular adhesion molecule-1 (ICAM-1). These findings suggest that the amelioration of MCT-induced pulmonary vascular remodeling and lung inflammation by PCPA is associated with the downregulation of Tph-1, SERT, MMP/TIMP and inflammatory cytokine expression in rats.
Databáze: OpenAIRE
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