title: [Effects of Yiqi Huayu prescription on knee cartilage degeneration in HIF-1alpha gene knockout mice].
abstract: OBJECTIVE
  To study the role of hypoxia-inducible factor 1 alpha (HIF1alpha) on knee cartilage degeneration,and to explore the effects and mechanisms of Chinese herbal compound Yiqi Huayu prescription on HIF-1alpha gene knockout mice on knee cartilage degeneration.
  
  
  METHODS
  The 4-month and 6-month HIF-1alpha gene knock out mice were obtained by interbreeding, and divided into HIF-1alpha +/+ 4-month mice group,HIF-1alpha -/- 4-month mice group,HIF-1alpha +/+ 6-month mice group and HIF-1alpha -/- 6-month mice group, 3 mice in each group. And then the 2-month-old HIF-1alpha gene knock out mice were randomly divided into Yiqi Huayu prescription group and physiological saline group. There were 6 mice in each group. After 2 months' drug administration, the knee joint of mice was collected, and the Mankin score were evaluated; Safranine-fast green staining, HE Staining, and immunohistochemistry analysis for VEGF, Col X, Col II, MMP-13 and Sox-9 were performed erespectively.
  
  
  RESULTS
  (1) Compared to the results in the HIF-1alpha+/+ mice groups, the HIF-1alpha-/- mice developed aging related cartilage loss and bony tissue appearance, cartilage defects increased,and cells reduced. In HIF-1alpha-/-4-month mice and 6-month mice group, the expresion of Col II and Sox9 decreased, and the expression of Col X, MMP-13 and VEGF increased. (2) Compared to the physiological saline group, the ossification and defect of knee joint cartilage reduced of mice in the Yiqi Huayu prescription group, the cartilage cell distribution was more uniform, and the total number of cells increased. The expression of type II collagen and Sox9 protein increased, expression of Col X, MMP-13 and VEGF protein decreased of mice in the Yiqi Huayu prescription group.
  
  
  CONCLUSIONS
  The knee cartilage degenerates in the HIF-1alpha cKO mice, and the degeneration increased with age adding. The Yiqi Huayu prescription can delay the degeneration of knee cartilage of HIF-1alpha cKO mice.
authors.affiliation: Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.forename: Fang-Fang
authors.initials: FF
authors.lastname: Dong
authors.forename: Xiao-Feng
authors.initials: XF
authors.lastname: Li
authors.forename: Bing
authors.initials: B
authors.lastname: Shu
authors.forename: Qi
authors.initials: Q
authors.lastname: Shi
authors.forename: Yong-Jun
authors.initials: YJ
authors.lastname: Wang
authors.forename: Chong-Jian
authors.initials: CJ
authors.lastname: Zhou
mesh_terms: D000818:Animals; D002357:Cartilage Diseases / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000172:deficiency / Q000235:genetics*; D007592:Joint Diseases / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D007719:Knee Joint / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D051379:Mice; D018345:Mice, Knockout
chemical_list: D004365:Drugs, Chinese Herbal; D051795:Hypoxia-Inducible Factor 1, alpha Subunit