title: [Expression of sonic hedgehog signaling pathw ay and its inhibition by cyclopamine in rat liver with chronic fluorosis].
abstract: OBJECTIVE
  To investigate the expression of sonic hedgehog (Shh) signaling pathway in liver fluorosis and to explore related mechanism.
  
  
  METHODS
  To establish animal model, 48 normal SD rats (aged 4-5 weeks) were randomly divided into 4 groups (12 each): control group, fluoriosis group, blocking group and blocking control group. After 6 months, the blocking group and blocking control group were injected intraperitoneally once every 2 days for 3 times with 10 mg/kg cyclopamine or dimethysulfoxide, respectively. Rats were sacrificed at the end of the experiment and the fluoride content in urine and liver function was determined. The expression of Shh and Gli1 protein and mRNA in hepatocytes was detected by immunohistochemistry and real-time fluorescence quantitative PCR, respectively.
  
  
  RESULTS
  The fluoride contents in the urine and the incidence of dental fluorosis increased in the fluoride and blocking control groups as compared with those in the control group, but decreased in the blocking group compared with those of the fluoride and blocking control group. Compared with the control group, the titers of aspartate transaminase (AST) and alanine transaminase (ALT) significantly increased, while the activity of total protein and albumin decreased in the fluoride and blocking control groups. Compared with the fluoride and blocking control groups, the activity of the ALT slightly declined and the AST, total protein and albumin slightly increased in the blocking group. Histologically, the cells were disorganized and swollen with cytoplasmic clearing (balloon cells), compared with the control group. The expression of Shh and Gli1 significantly increased in all but the control group. Compared with the fluoride and blocking control groups, the expression of Shh and Gli1 declined in the blocking group.
  
  
  CONCLUSIONS
  The overexpression and cyclopamine inhibition of the Shh signaling pathway are closely related to the content of fluoride in the liver. The Shh signaling pathway plays an important role in the pathogenesis of liver injury caused by fluorosis, suggesting a preventive and therapeutic target of the disease.
authors.affiliation: Department of Pathology, Guiyang Medical College, Guiyang 550004, China.
authors.forename: Lina
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Department of Pathology, Guiyang Medical College, Guiyang 550004, China. E-mail: gyyxyb12010@163.com.
authors.forename: Yanni
authors.initials: Y
authors.lastname: Yu
authors.affiliation: Department of Pathology, Guiyang Medical College, Guiyang 550004, China.
authors.forename: Chaonan
authors.initials: C
authors.lastname: Deng
mesh_terms: D000410:Alanine Transaminase / Q000032:analysis; D000818:Animals; D001219:Aspartate Aminotransferases / Q000032:analysis; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D004195:Disease Models, Animal; D005458:Fluoride Poisoning / Q000188:drug therapy / Q000378:metabolism*; D009050:Fluorosis, Dental / Q000175:diagnosis; D053823:Hedgehog Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D022781:Hepatocytes / Q000378:metabolism*; D051741:Kruppel-Like Transcription Factors / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008107:Liver Diseases / Q000188:drug therapy / Q000378:metabolism*; D012333:RNA, Messenger; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D014704:Veratrum Alkaloids / Q000494:pharmacology*; D000071676:Zinc Finger Protein GLI1
chemical_list: C498521:Gli1 protein, rat; D053823:Hedgehog Proteins; D051741:Kruppel-Like Transcription Factors; D012333:RNA, Messenger; C546888:Shh protein, rat; D014704:Veratrum Alkaloids; D000071676:Zinc Finger Protein GLI1; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D004121:Dimethyl Sulfoxide; C000541:cyclopamine