California National Primate Research Center, Davis, CA, USA.
Department of Internal Medicine, Division of Pulmonary and Critical Care, University of California, Davis, CA, USA.
Toxicol Appl Pharmacol. 2015 Feb 15;283(1):35-41. doi: 10.1016/j.taap.2014.12.006. Epub 2014 Dec 27.
In rhesus macaques, previous studies have shown that episodic exposure to allergen alone or combined with ozone inhalation during the first 6 months of life results in a condition with many of the hallmarks of asthma. This exposure regimen results in altered development of the distal airways and parenchyma (Avdalovic et al., 2012). We hypothesized that the observed alterations in the lung parenchyma would be permanent following a long-term recovery in filtered air (FA) housing. Forty-eight infant rhesus macaques (30 days old) sensitized to house dust mite (HDM) were treated with two week cycles of FA, house dust mite allergen (HDMA), ozone (O3) or HDMA/ozone (HDMA+O3) for five months. At the end of the five months, six animals from each group were necropsied. The other six animals in each group were allowed to recover in FA for 30 more months at which time they were necropsied. Design-based stereology was used to estimate volumes of lung components, number of alveoli, size of alveoli, distribution of alveolar volumes, interalveolar capillary density. After 30 months of recovery, monkeys exposed to HDMA, in either group, had significantly more alveoli than filtered air. These alveoli also had higher capillary densities as compared with FA controls. These results indicate that early life exposure to HDMA alone or HDMA+O3 alters the development process in the lung alveoli.
在恒河猴中,先前的研究表明,在生命的前 6 个月中,单独或与臭氧吸入联合进行的间歇性过敏原暴露会导致许多哮喘特征的疾病。这种暴露方案会导致远端气道和实质的发育改变(Avdalovic 等人,2012 年)。我们假设,在过滤空气(FA)住房中长期恢复后,肺部实质中观察到的改变将是永久性的。48 只恒河猴(30 天大)对屋尘螨(HDM)致敏,用 FA、屋尘螨过敏原(HDMA)、臭氧(O3)或 HDMA/臭氧(HDMA+O3)进行为期两周的周期治疗,持续五个月。在五个月结束时,每组中的六只动物进行尸检。每组中的另外六只动物被允许在 FA 中恢复 30 个月,届时它们将进行尸检。基于设计的体视学用于估计肺成分的体积、肺泡数量、肺泡大小、肺泡体积分布、肺泡间毛细血管密度。在恢复 30 个月后,暴露于 HDMA 的猴子,无论是在哪个组中,其肺泡数量都明显多于过滤空气。与 FA 对照组相比,这些肺泡的毛细血管密度也更高。这些结果表明,生命早期单独或联合暴露于 HDMA+O3 会改变肺肺泡的发育过程。