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

衰老和吸烟被认为是肺气肿和呼吸道炎症的主要致病因素。我们利用了两个携带固有衰老因子的小鼠品系(S)、衰老加速小鼠(SAM)P1品系和衰老标记蛋白-30(SMP30)基因敲除小鼠(SMP30Y/-)。SMP30是一种多功能蛋白质，可保护细胞功能免受年龄相关性恶化的影响。SAMP1和SMP30Y/-小鼠都被认为是老年肺的模型，因为它们的肺与年龄相关的肺泡扩大，没有明显的实质破坏。我们在两个菌株中评估了香烟烟雾引起的呼吸道炎症、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。尽管小鼠暴露在香烟烟雾中8周，但与对照品系(分别为SAMR1和SMP30Y/+)相比，组织病理学检查没有发现任何明显的呼吸道炎症和重塑，但它们确实出现了烟雾诱导的肺气肿。在SMP30Y/-小鼠的肺中，蛋白质羰基随着年龄的增长而增加，并且显著高于年龄匹配的SMP30Y/+小鼠。香烟烟雾暴露8周后，SMP30Y/-小鼠肺细胞蛋白质羰基、丙二醛、总谷胱甘肽和细胞凋亡率显著增加。这些结果表明，SMP30在调节与肺部衰老和吸烟相关的氧化应激方面发挥着重要作用。在肺组织的基因表达谱中，热休克蛋白68基因表达下调，I1-1β和CYP2C39基因表达上调，可能值得进一步研究它们在烟雾诱导的肺部炎症中的作用。

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.