title: [Effects of Bushen Wenyang Huayu Recipe on Expressions of HIF-1α, PHD2, and VHL in Endometriosis Rats with Shen Yang Deficiency Blood Stasis Syndrome].
abstract: OBJECTIVE
  To observe the effect of Bushen Wenyang Huayu Recipe (BWHR) on hypoxia inducible factor-1α (HIF-1α), proline hydroxylase2 (PHD2), von Hippel Lindau disease (VHL) suppressor gene expressions in endometriosis (EM) rats with Shen yang deficiency blood stasis syndrome (SYDBSS), and to explore the pathogenesis of EM and the mechanism of BWHR for treating EM.
  
  
  METHODS
  Totally 50 SD rats were randomly divided into five groups, i.e., the blank control group, the sham-operation group, the model group, the Chinese medicine (CM) group, and the Western medicine (WM) group, 10 in each group. Rats in the blank control group and the sham-operation group were fed routinely. Rats in the rest 3 groups received 30-day "extended refrigerator freezing and ice water immersion" and combined with " autotransplantation" to establish EM rat model with SYDBSS. One Milliliter BWHR at 3.33 g/mL was administered to rats in the CM group by gastrogavage. Gestrinone at the daily dose of 0. 5 mg/kg was administered to rats in the WM group by gastrogavage. Equal volume of normal saline was administered to rats in the model group, the blank control group, and the sham-operation group. The size and morphology of ectopic foci in rats were observed after 4 weeks of medication. Expressions of serum CA125, plasma cyclic adenosine monophosphate (cAMP), and plasma cyclic guanosine monophosphate (cGMP) were detected by radioimmunoassay. Morphological changes of eutopic endometrium and ectopic tissue were observed under the optical microscope by HE staining. Protein expressions and contents of HIF-lα, PHD2, and VHL were detected by immunohistochemical SABC method and Western blot. mRNA expressions of HIF-1α, PHD2, and VHL were detected by RT-PCR.
  
  
  RESULTS
  The ectopic foci grew significantly in the model group. Their volumes were obviously contracted after treated by CM and WM. Compared with the blank control group and the sham-operation group, serum CA125 and plasma cGMP obviously increased, cAMP obviously decreased (P < 0.05); expressions and contents of HIF-1α mRNA and protein all decreased (P < 0.05); mRNA and protein expressions and contents of PHD2 and VHL all decreased in the model group (P < 0.05). Compared with model group, levels of CA125 and cGMP obviously decreased; cAMP levels obviously increased, expressions and contents of HIF-1α mRNA and protein all increased, mRNA and protein expressions and contents of PHD2 and VHL all increased in the WM group and the CM group (P < 0.05). Compared with the CM group, PHD2 protein contents were higher in the WM group (P < 0.05). HIF-1α was negatively correlated with PHD2 (r = -0.799, P = 0.00). HIF-1α was negatively correlated with VHL (r = -0. 625, P = 0.003).
  
  
  CONCLUSIONS
  BWHR could effectively treat EM. Its mechanism might be associated with reducing contents of HIF-1α, serum CA125, and plasma cGMP, and up-regulating expressions of PHD2, VHL, and cAMP.
authors.forename: Yun-bo
authors.initials: YB
authors.lastname: Jia
authors.forename: Hui-lan
authors.initials: HL
authors.lastname: Du
authors.forename: Xing
authors.initials: X
authors.lastname: Gao
authors.forename: Wen-hui
authors.initials: WH
authors.lastname: Bian
authors.forename: Xiao-hua
authors.initials: XH
authors.lastname: Lin
authors.forename: Guang-guo
authors.initials: GG
authors.lastname: Ban
authors.forename: Qian-hua
authors.initials: QH
authors.lastname: Tian
mesh_terms: D000818:Animals; D000242:Cyclic AMP; D004365:Drugs, Chinese Herbal / Q000627:therapeutic use*; D004715:Endometriosis / Q000188:drug therapy* / Q000378:metabolism; D005260:Female; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D011392:Proline / Q000378:metabolism*; D012333:RNA, Messenger; D051381:Rats; D017207:Rats, Sprague-Dawley; D015854:Up-Regulation; D016711:Yang Deficiency / Q000188:drug therapy* / Q000378:metabolism
chemical_list: D004365:Drugs, Chinese Herbal; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D012333:RNA, Messenger; D011392:Proline; D000242:Cyclic AMP