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Patho-pharmacological Study of the Femoral Head Avascular Necrosis of Spontaneously Hypertensive Rats -Especially in the Effect on Epithelium by Steroid Hormone at Onset

Research Project

Project/Area Number 13671519
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Orthopaedic surgery
Research InstitutionNagasaki University Hospital

Principal Investigator

KUMAGAI Kenji  University Hospital, Assistant, 医学部附属病院, 助手 (00315235)

Co-Investigator(Kenkyū-buntansha) NIWA Masami  School of Medicine, Professor, 大学院・医歯薬総合研究科, 教授 (20136641)
Project Period (FY) 2001 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2002: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2001: ¥2,200,000 (Direct Cost: ¥2,200,000)
Keywordsstroke-prone spontaneously hypertensive rats / Osteonecrosis of the femoral head / Endothelium / NOS inhibitor / Steroid horumone / Hyperlipemia / 自然発症高血圧ラット / SHRSP
Research Abstract

Stroke-prone spontaneously hypertensive rats (SHRSP) are thought to be an animal model of osteonecrosis of the femoral head (ONFH). Studies for human ONFH and animal models have indicated that steroid hormone-induced hyperlipemia causing swollened adipocyts and endothelium dysfunctions is related to the etiology of this necrosis. Human ONFH, complicated by a high dose of steroid hormone-therapy, is a major side effect of organ transplantation. Our previous studies revealed that ONFH was observed in SHRSP at 15 to 20 weeks of age, and chronic ingestion of an NOS inhibitor inhibited the onset of the disease. To clarify the participation of hyperlipemia as an etiological factor in the disease, we examined the onset of ONFH in a new animal model of SHRSP fed a high fat and high cholesterol diet (HFC) containing N^G-nitro-L-arginine (L-NNA), as an NOS inhibitor. SHRSP with an administration of steroid hormone was used for the purpose of comparison.
Male SHRSP/Nagasaki, maintained and bred at … More the Laboratory Animal Center for Biomedical Research, Nagasaki University School of Medicine were used. At 15 weeks of age, rats were put at random into groups of 30, 25 and 24. The first group of 30 rats were fed the HFC diet containing L-NNA in a dose of 0.006% (HFC-NNA group). The second group of 25 was fed the SP diet (Funabashi Farm Co., Chiba, Japan), and at 17 weeks of age, 5 or 10 mg of methylpredonisolone was subcuatneously injected into the second group of rats (Steroid group). The third group of 24 rats, given the SP diet with no drug, served as controls. The rats were decapitated at 19 weeks of age.
The incidence of ONFH in the Steroid group was 50%, but it was lower in the HFC-NNA group and the control SHRSP. Numerous adipocytes in the metaphysial bone marrow of the HFC-NNA group and the Steroid group was observed microscopically. In the Steroid group, we noted the epiphysial bone marrow was filled with massive swollen adipocytes. In addition, there was a migration of swollen fatty cells into the necrotic area in the epiphysial bone marrow of the Steroid group. 94.0% of this group also demonstrated osteonecrosis and/or swollen adipocytes.
Epidemiological investigations for human ONFH has suggested that steroid hormone and alcohol intake are etiological factors related to the avascular necrosis of femoral head. We observed here the highest incidence of ONFH in the Steroid group. A hyperlipemia-induced increase in the number and invasion to necrotic areas of adipocytes seems to be an etiological factor, however, a lower incidense was observed in the HFC-NNA group with hypercholesterolemia. We admit that other mechanisms may be operative in the experimental model of femoral head avascular necrosis. Less

Report

(3 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • Research Products

    (20 results)

All Other

All Publications (20 results)

  • [Publications] Kenji Kumagai, Masami Niwa, et al.: "Osteonecrosis of Femoral Head in the Stroke Prone Spontaneously Hypertensive Rats"Clinical and Experimental Hypertention. 24・5. 477-478 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kenji Kumagai, Masahiro Wada, Masami Niwa, et al.: "Osteonecrosis of the Femoral Head in Spontaneously Hypertensive Rat (SHR) Strains"Clinical and Experimental Hypertention. 23・5. 408-408 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 熊谷 謙治, 丹羽 正美: "SHR大腿骨頭壊死に関する研究-NOS inhibitorおよびステロイドホルモン負荷の試み"厚生労働省特定疾患対策研究事業 骨・関節系調査研究班 特発性大腿骨頭壊死症調査研究分科会 平成14年度研究報告書. 57-64 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Masahiro Wada, Kenji Kumagai, Masami Niwa, et al.: "Effect of Warfarin on Spontaneously Hypertensive Rats (SHR) with Osteonecrosis of the Femur"Clinical and Experimental Hypertention. 23・5. 409-410 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 熊谷 謙治, 丹羽 正美: "SHR大腿骨頭壊死モデルに於けるNOS inhibitorの影響"厚生労働省特定疾患対策研究事業 骨・関節系調査研究班 特発性大腿骨頭壊死症調査研究分科会 平成13年度研究報告書. 76-79 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kenji Kumagai, Masahiro Wada, Masami Niwa et al.: "Osteonecrosis of the Femoral Head in Spontaneously Hypertensive Rat (SHR) Strains"Clinical and Experimental Hypertention. 23・5. 408 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Masahiro Wada, Kenji Kumagai, Masami Niwa et al.: "Effect fo Warfarin on Spontaneously Hypertensive Rats (SHR) with Osteonecrosis of the Femur"Clinical and Experimental Hypertention. 23・5. 409-410 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kenji Kumagai, Masami Niwa et al.: "Osteonecrosis of Femoral Head in the Stroke Prone Spontaneously Hypertensive Rats"Clinical and Experimental Hypertention. 24・5. 477-478 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kenji Kumagai, Masami Niwa, et al.: "Osteonecrosis of Femoral Head in the Stroke Prone Spontaneously Hypertensive Rats"Clinical and Experimental Hypertention. 24・5. 477-478 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 熊谷 謙治, 丹羽 正美: "SHR大腿骨頭壊死に関する研究-NOS inhibitorおよびステロイドホルモン負荷の試み"厚生労働省特定疾患対策研究事業 骨・関節系調査研究班 特発性大腿骨頭壊死症調査研究分科会 平成13年度研究報告書. 57-64 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Abraham CS, Harada N, Deli MA, Niwa M.: "Transient forebrain ischemia increases the blood-brain barrier permeability for albumin in stroke-prone spontaneously hypertensive rats"Cell Mol Neurobiol.. 22・4. 455-462 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Harada N, Niwa M, et al.: "Endothelin-1 binding to endothelin receptors in the rat anterior pituitary gland : possible formation of an ETA-ETB receptor heterodimer"Cell Mol Neurobiol. 22・2. 207-226 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Nagayama Y, Niwa M, et al.: "A novel murine model of Graves' Hyperthyroidism with intramuscular injection of adenovirus expressing the thyrotropin receptor"Journal of Immunology. 168. 2789-2794 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kis B, Niwa M, et al.: "Cerebral endothelial cells are a major source of adrenomedullin"J Neuroendocrinol.. 14・4. 283-293 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kenji Kumagai, Masahiro Wada, Masami Niwa et al.: "Osteonecrosis of the Femoral Head in Spontaneously Hypertensive Rat (SHR) Strains"Clinical and Experimental Hypertention. 23・5. 408 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Masahiro Wada, Kenji Kumagai, Masami Niwa et al.: "Effect fo Warfarin on Spontaneously Hypertensive Rats (SHR) with Osteonecrosis of the Femur"Clinical and Experimental Hypertention. 23・5. 409-410 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Csongor S Abraham, Masami Niwa et al.: "Cerebral Ischemia-Reperfusion Induced by Transient Bilateral Carotid Occulusion Increases the Permeability of the B.B.B. in SHRSP"Clinical and Experimental Hypertention. 23・5. 379-380 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Deli MA, Abraham CS, Takahata H, Niwa M.: "Tissue plasminogen activator inhibits P-glycoprotein activity in brain endothelial cells"Eur J Pharmacol. 411・5. R3-R5 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Nagayama Y, Niwa M. et al.: "Targeting the replication of adenovirus to p53-defective thyroid carcinoma with a p53-regulated Cre/loxP system"Cancer Gene Ther. 8・1. 36-44 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kis B, Niwa M et al.: "Adrenomedullin in the cerebral circulation"Peptides. 22・11. 1825-1834 (2001)

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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