Analysis of airway inflammation and remodeling induced by chronic cigarette smoke exposure in mice lungs.

慢性香烟烟雾暴露引起的小鼠肺部气道炎症和重塑的分析。

• 批准号: 15390259
• 负责人: FUKUCHI Yoshinosuke
• 金额: $ 6.4万
• 依托单位: JUNTENDO UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15390259/
• 关键词: COPD; Emphysema; Airway Inflammation; Cigarette smoke exposure; Protein modification; Aging; SMP30; Senescence-accelerated mouse; 炎症性サイトカイン; 慢性喫煙曝露; ニトロチロシン; 粘液細胞

Aging and smoking are considered as major contributing factors for the development of pulmonary emphysema and airway inflammation. We utilized two mouse strains carrying intrinsic aging factor(s), senescence-accelerated mice (SAM) P1 strain and senescence marker protein-30 (SMP30) knockout (SMP30Y/-) mice. SMP30 is a multifunctional protein providing protection to cellular functions from age-associated deterioration. Both SAMP1 and SMP30Y/- mice are known as a model for senile lung since they have lungs with age-related airspace enlargement and no apparent parenchymal destruction. We evaluated in both strains cigarette smoke induced airway inflammation, emphysema, macromolecule modification by oxidative stress, and aging-related genes in the lungs. Although mice were exposed to cigarette smoke for 8 weeks, histopathological examinations did not detect any significant airway inflammation and remodeling as compared with control strains (SAMR1 and SMP30Y/+, respectively) while they did developed smoke-induced emphysema. In the lungs of SMP30Y/- mice, protein carbonyls tended to increase with aging and significantly higher than the age-matched SMP30Y/+ mice. The protein carbonyls, malondialdehyde, total glutathione, and apoptosis of lung cells were significantly increased after 8-week exposure to cigarette smoke in the SMP30Y/- mice. These results suggests that SMP30 plays important roles in regulating oxidative stress associated with aging and smoking in the lungs. In the gene expression profiles in the lungs of SAMP1, down-regulation of heat shock protein 68 gene as well as up-regulation of I1-1β and CYP2C39 genes were detected and may deserve for future investigation about their role in smoke-induce lung inflammation.

衰老和吸烟被认为是肺气肿和气道炎症发生的主要因素。我们使用了两种携带内在衰老因子的小鼠品系，即加速衰老小鼠（SAM）P1品系和衰老标记蛋白-30（SMP 30）敲除小鼠（SMP 30 Y/-）。SMP 30是一种多功能蛋白质，可保护细胞功能免受年龄相关的退化。SAMP 1和SMP 30 Y/-小鼠都被认为是老年肺的模型，因为它们的肺具有与年龄相关的空域扩大，并且没有明显的实质破坏。我们评估了香烟烟雾诱导的气道炎症、肺气肿、氧化应激引起的大分子修饰以及肺中与衰老相关的基因。尽管小鼠暴露于香烟烟雾中8周，但与对照菌株（分别为SAMR 1和SMP 30 Y/+）相比，组织病理学检查并未检测到任何明显的气道炎症和重塑，而它们确实出现了烟雾诱导的肺气肿。在SMP 30 Y/-小鼠的肺中，蛋白质羰基倾向于随着年龄的增长而增加，并且显著高于年龄匹配的SMP 30 Y/+小鼠。吸烟8周后，SMP 30 Y/-小鼠肺组织蛋白质羰基化、丙二醛、总谷胱甘肽和细胞凋亡显著增加。这些结果表明，SMP 30在调节与衰老和吸烟相关的肺氧化应激中起重要作用。在SAMP 1肺组织基因表达谱中，热休克蛋白68基因表达下调，I1-1β和CYP 2C 39基因表达上调，这可能是进一步研究SAMP 1在烟雾诱导的肺部炎症中的作用的基础。

项目成果

Senescence marker protein-30 knockout mouse as a novel murine model of senile lung

• DOI: 10.1111/j.1440-1827.2003.01603.x
• 发表时间: 2004-03-01
• 期刊: PATHOLOGY INTERNATIONAL
• 影响因子: 2.2
• 作者: Mori, T;Ishigami, A;Fukuchi, Y
• 通讯作者: Fukuchi, Y

日常診療におけるGOLDの位置付け

GOLD在日常医疗中的地位

• 发表时间: 2004
• 期刊: 内科 93
• 作者: 笠木聡;瀬山邦明;福地義之助
• 通讯作者: 福地義之助

病態を測る重症度分類,閉塞性肺疾患の新たな診療

测量病理状况的严重程度分类，阻塞性肺病的新治疗方法

• 发表时间: 2004
• 期刊: 臨床医 31
• 作者: 直木 純;守 博昭;熱田 了;福地義之助
• 通讯作者: 福地義之助

COPD in Japan: The Nippon COPD Epidemiology Study

• DOI: 10.1111/j.1440-1843.2004.00637.x
• 发表时间: 2004-11-01
• 期刊: RESPIROLOGY
• 影响因子: 6.9
• 作者: Fukuchi, Y;Nishimura, M;Zaher, C
• 通讯作者: Zaher, C

Hypoxia and hypercapnia affect contractile and histological properties of rat diaphragm and hind limb muscles.

• DOI: 10.1016/j.pathophys.2003.09.003
• 发表时间: 2004-07-01
• 期刊: Pathophysiology : the official journal of the International Society for Pathophysiology
• 作者: Shiota, Satomi;Okada, Takao;Fukuchi, Yoshinosuke
• 通讯作者: Fukuchi, Yoshinosuke