Control of interstitial pneumonia by reducing nitric oxide production

通过减少一氧化氮的产生来控制间质性肺炎

• 批准号: 09670607
• 负责人: SHIMOKATA Kaoru
• 金额: $ 1.86万
• 依托单位: Nagoya University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09670607/
• 关键词: nitric oxide; interstitial pneumonia; radiation

Radiation pneumonitis is a major complication of radiation therapy. To elucidate the mechanisms of radiation-induced pneumonitis, we studied nitric oxide (NO) produced from lung tissues using a model of unilaterally irradiated rats. Our results demonstrated that alveolar macrophages (AM) produced NO after irradiation, and the expression of inducible NO synthase (NOS) in both AM and alveolar epithelial cells was increased. Furthermore, the progression of radiation pneumonitis was reduced with the in vivo treatment of the NOS inhibitor N^G-nitro-L-arginine methyl ester (L-NAME). The effect of L-NAME was further confirmed by the inhibition of mRNA expression for procollagen-alpha_1 type III of the lung. With these results, NO produced from AM and alveolar epithelial cells after irradiation may be an important mediator in the progression of radiation pneumonitis.We measured CO concentration in expired air of healthy subjects. Reproducibility of the data was satisfactory and estimation of CO concentration in expired air was considered to be applicable in clinical situation.

放射性肺炎是放射治疗的主要并发症。为了阐明放射性肺炎的机制，我们使用单侧辐射的大鼠模型研究了肺组织产生的一氧化氮（NO）。我们的结果表明，肺泡巨噬细胞（AM）在辐射后产生NO，并且AM和肺泡上皮细胞中诱导型NO合酶（NOS）的表达增加。此外，NOS抑制剂N^G-硝基-L-精氨酸甲酯（L-NAME）的体内治疗减少了放射性肺炎的进展。 L-NAME 的作用通过抑制肺 III 型前胶原-α_1 mRNA 表达得到进一步证实。根据这些结果，辐射后AM和肺泡上皮细胞产生的NO可能是放射性肺炎进展的重要介质。我们测量了健康受试者呼出空气中的CO浓度。数据的重复性令人满意，呼出气体中CO浓度的估计被认为适用于临床情况。

项目成果

Nozaki Y.: "Nitric oxide as an inflammatory mediator of radiation pneumonitis in rats." American Journal of Physiology. 272. L651-L658 (1997)

Nozaki Y.：“一氧化氮作为大鼠放射性肺炎的炎症介质。”