title: [Effect of triptolide on the expression of matrix metalloproteinases 2 and 9 in lungs of experimental pulmonary hypertension].
abstract: OBJECTIVE
  It has been shown that triptolide can attenuate pulmonary arterial hypertension in rats. This study was designed to investigate the therapeutic effect of triptolide on pulmonary hypertension in rats and possible mechanisms.
  
  
  METHODS
  Sixty Sprague-Dawley (SD) rats were randomly divided into 6 groups: normal control, model, continuous triptolide-treated, delayed triptolide-treated and two placebo groups for continuous and delayed fashions (n=10 each). The rats from the last 5 groups were injected with monocrotaline (MCT, 60 mg/kg) on day 7 after left pneumonectomy. The rats in the continuous triptolide-treated group received therapy from day 5 to 35 with triptolide (0.25 mg/kg intraperitoneally, every other day) and those in the delayed triptolide-treated received therapy with triptolide (0.20 mg/kg intraperitoneally, daily) from day 21 to 35 after operation. The hemodynamic parameters were detected by catheterization and the pathologic changes of small pulmonary arteries were evaluated by light microscopy 5 weeks post-operation. The expression of matrix metalloproteinases (MMPs) was assessed by immunohistochemistry and quantitative fluorescence PCR of relevant (MMP2 and MMP9) mRNAs.
  
  
  RESULTS
  By day 35 after operation, the mean pulmonary arterial pressure (mPAP, 38.10+/-1.20 vs 16.70+/-1.16 mmHg)the ratio of right ventricle/left ventricle plus septum [RV/(LV+S), 62.45+/-5.28% vs 22.76 +/-3.01%] and the vessel obstructive scores (VOS, 1.736 +/-0.080 vs 0.000 +/-0.000) increased significantly in the Model group compared with those of the normal control group (P < 0.01). The expression of MMP2 and MMP9 and their mRNA expression in lung tissues obviously also elevated in the Model group (P < 0.05). The continuous and the delayed triptolide-treated groups had significantly lower mPAP (20.80+/-1.03 and 26.20+/-1.03 mmHg, respectively) and less right ventricular hypertrophy and pulmonary arterial neointimal formation compared with the model and the placebo groups. The two treated groups also demonstrated decreased expression of MMP2 and MMP9 and their mRNA expression in lung tissues. There were significant differences in mPAP, RV/(LV+S) and VOS between the two triptolide-treated groups.
  
  
  CONCLUSIONS
  Triptolide attenuates the development of pulmonary hypertention and right ventricular hypertrophy and promotes regression of pulmonary arterial neointimal formation in pneumonectomized rats that received MCT, possibly through an inhibition of MMPs activity.
authors.affiliation: Department of Pediatrics, West China Second Hospital, Sichuan University, Chengdu 610041, China. weiliisme@163.com
authors.forename: Li
authors.initials: L
authors.lastname: Wei
authors.forename: Tong
authors.initials: T
authors.lastname: Liu
authors.forename: Bin
authors.initials: B
authors.lastname: Liu
authors.forename: Xian-Min
authors.initials: XM
authors.lastname: Wang
authors.forename: Liang
authors.initials: L
authors.lastname: Zhao
authors.forename: Tong-Fu
authors.initials: TF
authors.lastname: Zhou
mesh_terms: D000818:Animals; D004224:Diterpenes / Q000494:pharmacology* / Q000627:therapeutic use; D004852:Epoxy Compounds / Q000494:pharmacology / Q000627:therapeutic use; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000201:enzymology; D007150:Immunohistochemistry; D008168:Lung / Q000201:enzymology*; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000032:analysis* / Q000235:genetics; D020780:Matrix Metalloproteinase 9 / Q000032:analysis* / Q000235:genetics; D010616:Phenanthrenes / Q000494:pharmacology* / Q000627:therapeutic use; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D004224:Diterpenes; D004852:Epoxy Compounds; D010616:Phenanthrenes; D012333:RNA, Messenger; C001899:triptolide; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9