フルテキストURL | |
著者 |
Shimzu, K.
Okayama Univ, Grad Sch Med & Dent, Dept Anesthesiol & Resuscitol
Takahashi, T.
Okayama Univ, Grad Sch Med & Dent, Dept Anesthesiol & Resuscitol
Iwasaki, T.
Okayama Univ, Grad Sch Med & Dent, Dept Anesthesiol & Resuscitol
Shimizu, H.
Okayama Univ, Grad Sch Med & Dent, Dept Anesthesiol & Resuscitol
Inoue, K.
Okayama Univ, Grad Sch Med & Dent, Dept Anesthesiol & Resuscitol
Morimatsu, H.
Okayama Univ, Grad Sch Med & Dent, Dept Anesthesiol & Resuscitol
Omori, E.
Okayama Univ, Grad Sch Med & Dent, Dept Anesthesiol & Resuscitol
Matsumi, M.
Okayama Univ, Grad Sch Med & Dent, Dept Anesthesiol & Resuscitol
Akagi, R.
Okayama Prefectural Univ, Dept Nutr Sci
Morita, K.
Okayama Univ, Grad Sch Med & Dent, Dept Anesthesiol & Resuscitol
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抄録 | Treatment of rats with monocrotaline (MCT), a pyrrolizidine alkaloid plant toxin, is known to cause pulmonary hypertension (PH), and it has been used as a useful experimental model of PH. Recent findings suggested that pulmonary inflammation may play a significant role in the pathogenesis of MCT-induced PH. We also demonstrated that, following MCT administration to rats, there was a significant and sustained increase in the pulmonary expression of heme oxygenase-1 (HO-1), which is known to be induced by various oxidative stresses, including inflammation and free heme, and is thought to be essential in the protection against oxidative tissue injuries. In this study, we administered hemin (ferriprotoporphyrin chloride, 30 mol/kg b.w., subcutaneously), a potent inducer of HO-1, every 3 days to rats following subcutaneous administration of MCT (60 mg/kg) and examined its effect on MCT-induced PH and pulmonary inflammation. MCT administration caused pulmonary arterial wall thickening with marked elevation of right ventricular pressure, in association with prominent pulmonary inflammation as revealed by the increase in gene expression of tumor necrosis factor-alpha and the number of infiltrated neutrophils in the lung. In contrast, hemin treatment of MCT-administered animals, which led to a further increase in pulmonary HO-1 mRNA expression, significantly ameliorated MCT-induced PH as well as tissue inflammation. These findings suggest that hemin treatment ameliorates MCT-induced PH possibly mediated through induction of pulmonary HO-1 which leads to the attenuation of pulmonary inflammation.
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キーワード | Heme oxygenase-1
hemin
inflammation
monocrotaline
pulmonary hypertension
tumor necrosis factor-alpha
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発行日 | 2008-11
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出版物タイトル |
Medicinal Chemistry
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巻 | 4巻
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号 | 6号
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開始ページ | 572
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終了ページ | 576
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ISSN | 1573-4064
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資料タイプ |
学術雑誌論文
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オフィシャル URL | http://dx.doi.org/10.2174/157340608786241972
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関連URL | http://ousar.lib.okayama-u.ac.jp/metadata/50651
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言語 |
英語
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論文のバージョン | author
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査読 |
有り
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DOI | |
Web of Science KeyUT |