title: [Effects of Chinese herbal medicine Yiqi Huoxue Formula on TGF-β/smad signal transduction pathway and connective tissue growth factor in rats with renal interstitial fibrosis].
abstract: OBJECTIVE
  To observe the effects of Yiqi Huoxue Formula (YQHXF), a compound Chinese herbal medicine, on transforming growth factor-β (TGF-β)/smad signal transduction pathway and connective tissue growth factor (CTGF) in rats with renal interstitial fibrosis
  
  
  METHODS
  Unilateral ureteral obstruction (UUO) rat model was established and the rats were randomly divided into 5 groups: untreated group, high-, medium-, and low-dose YQHXF groups and fosinopril sodium group. Another group with sham operation was set as control. All rats were administered with corresponding drugs for 3 weeks. After the last administration, each rat was sacrificed and weighed and the serum was separated for creatinine (Cr) and blood urea nitrogen (BUN) detection. Kidneys of the rats were taken out, and mRNA and protein expressions of TGF-β, smad2, smad7 and CTGF were measured with real-time fluorescent quantitative reverse transcription-polymerase chain reaction and Western blotting respectively; fibrosis of the kidney tissue was observed with hematoxylin-eosin (HE) staining and Masson trichrome staining.
  
  
  RESULTS
  Compared with sham-operation group, Cr and BUN in serum of UUO groups were increased, while high-dose YQHXF treatment decreased the UUO-induced increase of Cr and BUN levels. HE staining and Masson staining results showed that the renal tubular epithelial cells in untreated group got atrophied; lumens of renal tubules expanded; fibroplastic proliferation and inflammatory cell infiltration were observed in renal interstitium; the number of glomerulus decreased and collagen increased significantly compared with sham-operation group. In the high- and medium-dose YQHXF groups and fosinopril sodium group, the histopathological changes of inflammatory cell infiltration, fibroplastic proliferation, expansion of lumens of renal tubules was improved as compared with the untreated group. The mRNA and protein expressions of TGF-β, smad2 and CTGF in untreated group were higher than those in sham-operation group (P<0.05), and the mRNA and protein expressions of smad7 in untreated group were lower than those in the sham-operation group (P<0.05). Compared with untreated group, high- and medium-dose of YQHXF significantly down-regulated the mRNA and protein expressions of TGF-β, smad2 and CTGF (P<0.01, P<0.05), and up-regulated the mRNA and protein expressions of smad7 (P<0.01, P<0.05).
  
  
  CONCLUSIONS
  The mRNA expression of CTGF in UUO rats may be regulated by TGF-β/smad signaling transduction pathway. YQHXF might inhibit the expression of CTGF through down-regulation of TGF-β and smad2 and up-regulation of smad7, thus inhibiting the progression of renal interstitial fibrosis.
authors.affiliation: Department of Molecular Biology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China.
authors.forename: Yong-mei
authors.initials: YM
authors.lastname: Liu
authors.forename: Rui-hua
authors.initials: RH
authors.lastname: Liu
authors.forename: Wen-jun
authors.initials: WJ
authors.lastname: Liu
authors.forename: Li
authors.initials: L
authors.lastname: Liu
authors.forename: Zhi-kui
authors.initials: ZK
authors.lastname: Wu
authors.forename: Yu-ying
authors.initials: YY
authors.lastname: Chen
mesh_terms: D000818:Animals; D055513:Connective Tissue Growth Factor / Q000378:metabolism*; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D005355:Fibrosis; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D007674:Kidney Diseases / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008517:Phytotherapy; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction; D051785:Smad Proteins / Q000378:metabolism*; D051899:Smad2 Protein / Q000378:metabolism; D051906:Smad7 Protein / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism*
chemical_list: C526316:CCN2 protein, rat; D004365:Drugs, Chinese Herbal; D051785:Smad Proteins; D051899:Smad2 Protein; C497784:Smad2 protein, rat; D051906:Smad7 Protein; C497808:Smad7 protein, rat; D016212:Transforming Growth Factor beta; D055513:Connective Tissue Growth Factor; C033946:yiki-huoxue