ラット4型コラーゲンの組換えNC1抗原感作による糸球体腎炎モデルにおける腎機能および組織構造の変化

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概要

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• The aim of this study was to develop and characterize a rat glomerulonephritis model, which progresses to renal fibrosis and renal failure. A single immunization of female WKY rats with more than 10 μg of recombinant α3(IV)NC1 protein caused severe proteinuria followed by progressive increases in plasma creatinine and blood urea nitrogen (BUN) level within 42 days. Sequential histopathological evaluation revealed crescent formation in glomeruli followed by tubular dilation and interstitial fibrosis. Hydroxyproline content and expression of type I collagen and smooth muscle actin genes in the renal cortex increased as renal dysfunction progressed. Furthermore, the TGF-β1 level in the renal cortex also increased. In the evaluation of antinephritic agents in this model, prednisolone and mycophenolate mofetil (MMF) treatment significantly decreased plasma creatinine and BUN, and suppressed renal fibrosis and histological changes involving crescent formation, compared with the vehicle-treated nephritic rats, whereas lisinopril treatment failed to improve renal function and histology. We demonstrated that immunization of female WKY rats with a sufficient dose of recombinant α3(IV)NC1 induces end-stage kidney disease accompanied by renal fibrosis. The relatively short period needed to induce the disease and the high incidence of functional and structural changes were considered a great advantage of this model for clarifying the mechanisms of progressive glomerulonephritis and for evaluating agents used to treat renal failure.

著者

• TAKIGUCHI Yoshiharu

  Department of Clinical Pharmacology, Subdivision of Clinical Pharmaceutical Sciences, Institute of H

• 西林 政治

  Quests Research Institute, Otsuka Pharmaceutical Co., Ltd.

• 平野 隆弘

  First Institute of New Drug Discovery, Otsuka Pharmaceutical Co., Ltd.

• 上原 憲二

  First Institute of New Drug Discovery, Otsuka Pharmaceutical Co., Ltd.

• UEHARA Kenji

  First Institute of New Drug Discovery, Otsuka Pharmaceutical Co., Ltd.

• NAKANO Yoshimasa

  First Institute of New Drug Discovery, Otsuka Pharmaceutical Co., Ltd.

• AIHARA Miki

  First Institute of New Drug Discovery, Otsuka Pharmaceutical Co., Ltd.

• YAMADA Yoshihisa

  First Institute of New Drug Discovery, Otsuka Pharmaceutical Co., Ltd.

• MURAGUCHI Masahiro

  Institute of Biomedical Innovation, Otsuka Pharmaceutical Co., Ltd.

• IWATA Fusako

  Institute of Biomedical Innovation, Otsuka Pharmaceutical Co., Ltd.

• HIRANO Takahiro

  First Institute of New Drug Research, Otsuka Pharmaceutical Co., Ltd.

• Hirano Takahiro

  First Inst. Of New Drug Discovery Otsuka Pharmaceutical Co. Ltd.

• Uehara Kenji

  First Inst. Of New Drug Discovery Otsuka Pharmaceutical Co. Ltd.

• HATTORI Katsuji

  First Institute of New Drug Discovery, Otsuka Pharmaceutical

• Yamada Yoshihisa

  First Inst. Of New Drug Discovery Otsuka Pharmaceutical Co. Ltd.

• Takiguchi Yoshiharu

  Department Of Clinical Pharmacology Institute Of Health Biosciences The University Of Tokushima Grad

• Nakano Yoshimasa

  First Inst. Of New Drug Discovery Otsuka Pharmaceutical Co. Ltd.

• Hattori Katsuji

  First Inst. Of New Drug Discovery Otsuka Pharmaceutical Co. Ltd.

• NISHIBAYASHI Seiji

  Quests Research Institute, Otsuka Pharmaceutical Co., Ltd.

• Aihara Miki

  First Inst. Of New Drug Discovery Otsuka Pharmaceutical Co. Ltd.

• TAKIGUCHI Yoshiharu

  Department of Clinical pharmacology, Institute of Health Bioscience, The University of Tokushima Graduate School

• HIRANO Takahiro

  First Institute of New Drug Discovery, Otsuka Pharmaceutical Co., Ltd.

関連論文

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