Molecular and genetic studies on patho genesis and patho plrysiolegy of emphysema
肺气肿发病机制及病理学的分子遗传学研究
基本信息
- 批准号:11470142
- 负责人:
- 金额:$ 6.91万
- 依托单位:
- 依托单位国家:日本
- 项目类别:Grant-in-Aid for Scientific Research (B).
- 财政年份:1999
- 资助国家:日本
- 起止时间:1999 至 2000
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
Fawn-hooded rat (FHR) is a strain characterized by a distal air-space enlargement with increased lung distensibility although there was no alveolar wall destruction. In order tO analyze the effect of structural changes of lung parenchyma on the mechanical properties, the respiratory impedance (Z) was examined by utilizing a computer-controlled small-animal ventilator (Flexivent, Scireq, Canada) and compared with those of age-matched Wister kyoto control rats (WKY). The measured impedance Z was fit by the constant-phase model (Z=R+j(27πf)I+(Gtis-Htis)/(2πf)α), where R is airway resistance, Gtis is tissue resistance, and Htis is tissue elastance. TLC was significantly larger in FOR than in WKR (2.60±39 vs 1.97±0.22, p<0.01) and a leftward arid upward shift of the pressure-volume curve was observed in FHR with higher shape constant (K) value as compared with WKY (0.219±0.018 vs 0.117±0.011, p<0.01). Although there was no significant difference in R (airway resistance) between 2 groups, di … More minished Gtis and Htis were observed in FUR at low lung volume (p<0.05), but increased Gtis and Htis were observed at high lung volume (p<0.05) as compared with the WKY.These results suggest that FHR has a higher TLC with reduced lung elastic recoil and that these parechymal structural changes result in biphasic mechanical properties against lung volume in FHR.We are now trying to induce to develop pulmonary emphysema in FHR by exposing cigarette smoke for at least 16 weeks and then analyze cell population in bronchoalveolar lavage fluid, lung mechanics, arid pathology of the lungs. On the other hand, the effect of cigarette smoke on proteaseantiprotease balance in lung parenchyma was analyzed with special reference to matrix metalloproteinases (MMP) production from human macrophage-like cell lines (U937 and THP-1). When U937 cells were stimulated with D-nicotine or cigarette smoke extract (CSE), MMP-2 production by U937 was not affected by D-nicotine but increased by CSE in a dose-dependent manner. THP-1 cells showed increased MMP-9 production by CSE.All-trans retinoic acid and 9-cis retinoic acid suppressed PMA-mediated MMP-9 production by both cell lines and northern blot analysis revealed increased expression of RAR-α and FAR-γ by retinoid, suggesting that both RARs are involved in retinoid-mediated regulation of MMP-9 production by directly modulating gene expression. Less
Fawn-hooded大鼠(FHR)是一种以远端气腔扩大和肺扩张性增加为特征的品系,尽管没有肺泡壁破坏。为了分析肺实质结构变化对机械性能的影响,通过使用计算机控制的小动物呼吸机(Scireq,Canada)检测呼吸阻抗(Z),并与年龄匹配的Wister京都对照大鼠(WKY)的呼吸阻抗(Z)进行比较。通过恒定相位模型(Z=R+j(27πf)I+(Gtis-Htis)/(2πf)α)拟合测量的阻抗Z,其中R是气道阻力,Gtis是组织阻力,Htis是组织弹性。FHR的TLC明显大于WKY(2.60±39 vs 1.97±0.22,p<0.01),FHR的压力-容积曲线明显上移,形状常数(K)值明显高于WKY(0.219±0.018 vs 0.117±0.011,p<0.01)。虽然两组之间的R(气道阻力)无显著差异,但差异无统计学意义。 ...更多信息 在低肺容量时,FUR中观察到Gtis和Htis减小(p<0.05),但在高肺容量时观察到Gtis和Htis增加(p<0.05),但不影响正常人的生活。这些结果表明,FHR具有更高的TLC,肺弹性回缩减少,这些实质结构的变化导致FHR的双相机械性能与肺体积的关系。通过暴露香烟烟雾至少16周来观察FHR中的肺气肿,然后分析支气管肺泡灌洗液中的细胞群、肺力学和肺病理学。另一方面,香烟烟雾对肺实质中蛋白酶-抗蛋白酶平衡的影响进行了分析,特别是参考从人巨噬细胞样细胞系(U937和THP-1)的基质金属蛋白酶(MMP)的生产。当用D-尼古丁或香烟烟雾提取物(CSE)刺激U937细胞时,U937产生的MMP-2不受D-尼古丁的影响,但CSE以剂量依赖性方式增加。全反式维甲酸和9-顺式维甲酸可抑制PMA介导的MMP-9的产生,北方印迹分析显示类维生素A可增加RAR-α和FAR-γ的表达,提示类维生素A可通过直接调节基因表达来调节MMP-9的产生。少
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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FUKUCHI Yoshinosuke其他文献
FUKUCHI Yoshinosuke的其他文献
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{{ truncateString('FUKUCHI Yoshinosuke', 18)}}的其他基金
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 - 财政年份:2003
- 资助金额:
$ 6.91万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Cigarette smoke-induced lung pathology in SMP30 knockout mice
SMP30 基因敲除小鼠香烟烟雾诱发的肺部病理学
- 批准号:
13470130 - 财政年份:2001
- 资助金额:
$ 6.91万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Multidisciplinary study on the organ interrelation between swallowing and regulation of respiration for furthering the quqlity of life in the elderly
吞咽与呼吸调节之间的器官相互关系的多学科研究以提高老年人的生活质量
- 批准号:
07407016 - 财政年份:1995
- 资助金额:
$ 6.91万 - 项目类别:
Grant-in-Aid for Scientific Research (A)
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