title: [Effect of schisandrin B on lung mRNA expression of transforming growth factor-beta1 signal transduction molecule in rat lungs exposed to silica].
abstract: OBJECTIVE
  To investigate the effects of schisandrin B (Sch-B) on expression of transforming growth factor-beta1 (TGF-beta1) and signal transduction molecule mRNA in rat lungs exposed to SiO2, and explore the intervention mechanism of Sch-B on pulmonary fibrosis induced by SiO2.
  
  
  METHODS
  Ninety six Wistar rats were randomly divided into control (normal saline) group, SiO2 group and SiO2 plus Sch-B group. The rats were exposed to SiO2 by direct tracheal instillation to establish the silicotic animal models. SiO2 group and SiO2 plus Sch-B group were treated with 1 ml SiO2 (50 mg/ml) for each rat From the first day after model establishment, SiO2 plus Sch-B group were orally given Sch-B (80 mg/kg) a day, control group and silica group were orally given olive oil. On the 3rd, 7th, 14th and 28th days after treatment, 8 rats in each group were sacrificed and samples were collected. The histo-pathological examination of lung was performed by HE staining. The expression levels of TGF-beta1, TGF-betaR II and Smad4 mRNA in the lung tissues were detected by RT-PCR.
  
  
  RESULTS
  The results of histo-pathological examination showed that in SiO2 group, lung tissues were injured obviously; the alveolar inflammation with alveolus interval edema and inflammation cell infiltration appeared on the 3rd and 7th days; the alveolus interval became thicker, became thicker, fibroblast and collagen matrix increased markedly on 14th day; the alveolar structure was damaged, alveolar wall thickened obviously, collagen aggravation and pulmonary fibrosis displayed on 28th day. The alveolar inflammation and pulmonary fibrosis in SiO2 plus Sch-B group were significantly less than those in SiO2 group. The expressions levels of TGF-beta1 TGF-betaR II and Smad4 mRNA (TGF-1beta: 1.03 +/- 0.31, 1.33 +/- 0.39,1.08 +/- 0.26, 0.82 +/- 0.16, TGF-betaR II: 0.65 +/- 0.11, 0.80 +/- 0.16, 0.83 +/- 0.24, 0.62 +/- 0.15, Smad4:0.87 +/- 0.15, 0.68 +/- 0.11, 0.78 +/- 0.19, 0.30 +/- 0.08) in SiO2 group were significantly higher than those in the control group (TGF-beta1:0.59 +/- 0.22, 0.55 +/- 0.25, 0.56 +/- 0.20, 0.55 +/- 0.12, TGR-betaR II :0.28 +/- 0.13, 0.31 +/- 0.15, 0.34 +/- 0.15, 0.27 +/- 0.09, Smad4:0.23 +/- 0.11, 0.40 +/- 0.12, 0.39 +/- 0.12, 0.18 +/- 0.06) (P < 0.01 or P < 0.05), but the expression level of TGF-beta1 mRNA was the highest on the 7th day. The expression levels of TGF-beta1 and Smad4 mRNA (TGF-beta1:0.68 +/- 0.28, 0.88 +/- 0.25, 0.75 +/- 0.11, 0.61 +/- 0.14,Smad4:0.25 +/- 0.12, 0.45 +/- 0.09, 0.44 +/- 0.07, 0.21 +/- 0.04) in SiO2 plus Sch-B group were significantly lower than those in SiO2 group (P < 0.01 or P < 0.05 ), but there were no significant differences of the TGFbetaR II mRNA expression levels between SiO2 group and SiO2 plus Sch-B group.
  
  
  CONCLUSIONS
  Sch-B can reduce the pulmonary fibrosis induced by SiO2 through inhibition of the mRNA express of TGF-beta1 and Smad4 in the lung tissue, modulating the TGF-beta1/Smad4 signal transduction pathway and inhibiting the target gene activation.
authors.affiliation: Laboratory Animal Center of Shanxi Medical University, Taiyuan 030001, China.
authors.forename: Lin-Hua
authors.initials: LH
authors.lastname: Fan
authors.forename: Tian-Fu
authors.initials: TF
authors.lastname: Liu
authors.forename: Min
authors.initials: M
authors.lastname: Guo
authors.forename: Mao-Lin
authors.initials: ML
authors.lastname: Liu
authors.forename: Zhi-Ping
authors.initials: ZP
authors.lastname: Wang
authors.forename: Su-Jin
authors.initials: SJ
authors.lastname: Si
mesh_terms: D000818:Animals; D034242:Cyclooctanes / Q000494:pharmacology; D005260:Female; D017705:Lignans / Q000494:pharmacology*; D008168:Lung / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D008297:Male; D011083:Polycyclic Compounds / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects*; D012829:Silicosis / Q000378:metabolism* / Q000473:pathology; D051901:Smad4 Protein / Q000235:genetics / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism*
chemical_list: D034242:Cyclooctanes; D017705:Lignans; D011083:Polycyclic Compounds; D012333:RNA, Messenger; D051901:Smad4 Protein; C490811:Smad4 protein, rat; D053773:Transforming Growth Factor beta1; C015499:schizandrin B