title: [Early treatment with hepatocyte growth factor improves pulmonary artery and right ventricular remodeling in rats with pulmonary artery hypertension by modulating cytokines expression].
abstract: OBJECTIVE
  To investigate the effect of early treatment with hepatocyte growth factor (HGF) on the cytokine expression and pulmonary artery, right ventricular (RV) remodeling in the rat model of pulmonary artery hypertension (PAH).
  
  
  METHODS
  The rat model of PAH was produced by injecting monocrotaline, and the model rats were randomly divided into empty adenovirus transfection group (MCT group, n = 10) and HGF gene transfection group(HGF group, n = 10). Another group of rats served as the Sham operation group (Sham group n = 10). After 4 weeks of HGF gene transfection, the histological sections of the lungs and right ventricular (RV) were stained with hematoxylin-eosin (HE) and the pulmonary artery and RV remodeling were examined. The rat lung sections were also immunostained with antibodies against factor VIII, and the capillary density were calculated. Meanwhile, the mRNA expression of TNF-α, IL-6, IL-1β and TGF-β1 in pulmonary arteries and RV were detected by RT-PCR.
  
  
  RESULTS
  HGF gene treatment significantly decreased the ratio of vessel wall thickness to pulmonary artery diameter and the ratio of vessel wall area to total area, and increased the capillary density of lung in PAH rats. HGF gene treatment also significantly decreased cross-sectional area of cardiomyocytes and collagen deposited in RV. Moreover, HGF gene treatment significantly decreased the expression of cytokines in pulmonary artery (TNF-α: 0.82 ± 0.07 vs 0.49 ± 0.09, IL-6: 1.13 ± 0.19 vs 0.68 ± 0.09, IL-1β: 0.86 ± 0.11 vs 0.51 ± 0.07, TGF-β1: 1.18 ± 0.12 vs 0.59 ± 0.10) and RV (TNF-α: 0.79 ± 0.11 vs 0.48 ± 0.08, IL-6: 1.03 ± 0.11 vs 0.63 ± 0.09, IL-1β: 0.81 ± 0.11 vs 0.52 ± 0.07, TGF-β1: 0.94 ± 0.12 vs 0.53 ± 0.10) in MCT induced PAH rats (P < 0.05) .
  
  
  CONCLUSIONS
  Early treatment with HGF improves pulmonary artery and RV remodeling, possibly by decreasing the expression of TNF-α, IL-6, IL-1β and TGF-β1 in pulmonary arteries and RV.
authors.affiliation: Department of Paediatrics Heping Hospital, Changzhi Medical College, Changzhi, Shanxi 046000, China.
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Wang
authors.forename: Yongjin
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Email: hpyywxl@163.com.
authors.forename: Shuling
authors.initials: S
authors.lastname: Rong
authors.forename: Hongbiao
authors.initials: H
authors.lastname: Ma
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism*; D004195:Disease Models, Animal; D006352:Heart Ventricles / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D017228:Hepatocyte Growth Factor / Q000235:genetics* / Q000494:pharmacology; D006976:Hypertension, Pulmonary / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D016686:Monocrotaline / Q000009:adverse effects; D011651:Pulmonary Artery / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014162:Transfection; D020257:Ventricular Remodeling / Q000187:drug effects*
chemical_list: D016207:Cytokines; D017228:Hepatocyte Growth Factor; D016686:Monocrotaline