Variation in senescent-dependent lung changes in inbred mouse strains
Variation in senescent-dependent lung changes in inbred mouse strains
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DOI：
10.1152/japplphysiol.00833.2006
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发表时间：
2007-04-01
影响因子：
3.3
通讯作者：
Tankersley, Clarke G.
中科院分区：
文献类型：
--
作者：
Huang, Kewu;Mitzner, Wayne;Tankersley, Clarke G.
我们实验室以前的研究表明，近交系小鼠之间的肺发育存在差异。在本研究中，检查了C57 BL/6 J（136）和DBA/2 J（D2）品系在肺结构和功能方面的衰老依赖性差异。具体来说，我们假设，由于可识别的基因表达差异，肺的衰老变化各不相同。准静态压力-容积曲线和呼吸阻抗测量进行2和20月龄B6和D2小鼠。两种品系小鼠在30 cmH 2 O（V-30）压力下的肺体积均随年龄增长而显著增加（P < 0.01），但D2小鼠肺体积的增加比例（68%）大于B6小鼠（40%）。此外，在20月龄的D2小鼠中观察到50%V-30时弹性回缩压力降低和气道阻力随呼气末正压的降低，但在B6小鼠中未观察到。肺实质的形态计量学分析显示，两种品系小鼠的弹性纤维含量均随年龄增长而显著降低，但20月龄时，D2小鼠的胶原含量随年龄增长而显著增加（P < 0.01），而B6小鼠则无此现象。此外，使用定量RT-PCR方法，不同品系之间的基因表达差异表明，D2小鼠在20月龄时显著（P < 0.05）下调肺组织中弹性蛋白（Eln）和前胶原1、111和VI（Collal、Col 3al和Col 6a 3）的表达。这些年龄依赖性变化伴随着D2中基质金属蛋白酶9（Mmp 9）的基因表达增加和B6小鼠中基质金属蛋白酶的组织抑制剂（Timpl和Timp 4）的增加。总之，本研究的结果表明，两种菌株的肺力学表现出显着的年龄依赖性变化。然而，相对于B6小鼠，D2小鼠的变化加速。此外，基因表达差异似乎与肺力学特性的菌株特异性变化有关。
Previous studies from our laboratories showed lung development differences between inbred strains of mice. In the present study, the C57BL/6J (136) and DBA/2J (D2) strains were examined for senescent-dependent differences with respect to the lung structure and function. Specifically, we hypothesize that senescent changes in lung vary between strains due to identifiable gene expression differences. Quasi-static pressure-volume curves and respiratory impedance measurements were performed on 2- and 20-mo-old B6 and D2 mice. Lung volume at 30 cmH(2)O (V-30) pressure was significantly (P < 0.01) increased with age in both strains, but the increase was proportionally greater in D2 (68%) than in B6 (40%) mice. In addition, decreased elastic recoil pressure at 50% of V-30 and a reduction in airway resistance as a function of positive end-expiratory pressure were observed in 20-mo-old D2 mice but not in B6 mice. Morphometric analysis of lung parenchyma showed significant decreases in elastic fiber content with age in both strains, but the collagen content was significantly (P < 0.01) increased with age in D2 but not B6 mice at 20 mo. Furthermore, using quantitative RT-PCR methods, gene expression differences between strains suggested that D2 mice significantly (P < 0.05) downregulated the expressions of elastin (Eln) and procollagen 1, 111, and VI (Collal, Col3al, and Col6a3) in lung tissue at 20 mo of age. These age-dependent changes were accompanied by an increased gene expression in matrix metalloproteinase 9 (Mmp9) in D2 and an increase in tissue inhibitor of matrix metalloproteinase (Timpl and Timp4) in B6 mice. In conclusion, the results from the present study demonstrate that lung mechanics of both strains show significant age-dependent changes. However, changes in D2 mice are accelerated relative to B6 mice. Moreover, gene expression differences appear to be involved in the strain-specific changes of lung mechanic properties.