Department of Internal Medicine, Pulmonary and Critical Care Medicine, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390-9034, USA.
J Appl Physiol (1985). 2010 Dec;109(6):1913-9. doi: 10.1152/japplphysiol.00549.2010. Epub 2010 Aug 26.
The Zucker diabetic fatty (ZDF fa/fa) rat with genetic leptin insensitivity develops obesity and Type 2 diabetes mellitus (T2DM) with age accompanied by hyperplastic changes in the distal lung (Am J Physiol Lung Cell Mol Physiol 298: L392-L403, 2010). To determine the functional consequences of structural changes, we developed a rebreathing (RB) technique to simultaneously measure lung volume, pulmonary blood flow, lung diffusing capacity (Dl(CO)), membrane diffusing capacity (Dm(CO)), pulmonary capillary blood volume (Vc), and septal tissue volume in anesthetized tracheostomized male ZDF fa/fa and matched lean (+/+) control animals at 4, 8, and 12 mo of age. Results obtained by RB technique were compared with that measured by a single-breath (SB) technique and to that expected in a wide range of species. In fa/fa animals compared with +/+, lung volumes and compliance were 13-35% lower at different ages, and the normal age-related increase in lung compliance was no longer evident. Mean pulmonary blood flow declined with age in fa/fa but not in +/+ animals. Dl(CO) measured at a given pulmonary blood flow was 20-43% lower at different ages due to reductions in both Dm(CO) and Vc. Septal tissue volume was also reduced in older fa/fa rats. We conclude that obese rats with T2DM develop significant restrictive pulmonary defects with diffusion impairment in a pattern similar to that previously reported in obese human subjects with T2DM. Functional impairment became exaggerated with age and duration of T2DM. In both fa/fa and +/+ animals, Dl(CO) measured by RB was systematically higher than by SB technique whereas lung volume was similar, a finding consistent with heterogeneous distribution of ventilation in the rat lung.
Zucker 糖尿病肥胖（ZDF fa/fa）大鼠具有遗传性瘦素不敏感，随着年龄的增长会发展为肥胖和 2 型糖尿病（T2DM），同时远端肺部出现增生性改变（Am J Physiol Lung Cell Mol Physiol 298: L392-L403, 2010）。为了确定结构变化的功能后果，我们开发了一种再呼吸（RB）技术，以便同时测量麻醉气管切开雄性 ZDF fa/fa 和匹配的瘦（+/+）对照动物在 4、8 和 12 个月龄时的肺容积、肺血流、肺弥散量（Dl(CO)）、膜弥散量（Dm(CO)）、肺毛细血管血容量（Vc）和间隔组织体积。通过 RB 技术获得的结果与通过单次呼吸（SB）技术测量的结果以及在广泛物种中预期的结果进行了比较。与+/+相比，fa/fa 动物在不同年龄时的肺容积和顺应性低 13-35%，并且正常的年龄相关肺顺应性增加不再明显。fa/fa 动物的平均肺血流随年龄下降，但+/+动物的肺血流则没有下降。由于 Dm(CO)和 Vc 均降低，在不同年龄时，以给定肺血流测量的 Dl(CO)低 20-43%。老年 fa/fa 大鼠的间隔组织体积也减少。我们得出结论，患有 2 型糖尿病的肥胖大鼠出现明显的限制性肺缺陷，弥散功能障碍的模式类似于先前报道的患有 2 型糖尿病的肥胖人类患者。功能障碍随着 2 型糖尿病的年龄和持续时间的增加而加剧。在 fa/fa 和+/+动物中，通过 RB 测量的 Dl(CO)均高于 SB 技术，而肺容积则相似，这一发现与大鼠肺通气的异质性分布一致。
