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基于支气管肺发育不良设计的高氧早产兔模型中肺的立体学

2021-10-26 MedSci原创 MedSci原创

支气管肺发育不良(BPD)是一种与早产相关的慢性人类肺部疾病。在早期,BPD 被描述为呼吸窘迫综合征和治疗干预措施(包括通气和氧气供应)的综合作用的结果。

支气管肺发育不良(BPD)是一种与早产相关的慢性人类肺部疾病。在早期,BPD 被描述为呼吸窘迫综合征和治疗干预措施(包括通气和氧气供应)的综合作用的结果。随着外源性表面活性剂治疗早产儿的可能性,这种形式的 BPD(“旧 BPD”)已经减少;然而,新生儿护理的进步有助于让非常不成熟的新生儿存活下来,这些新生儿在妊娠 24 周和 28 周之间出生。在这个阶段,肺发育不完整,需要进步才能获得全部功能,同时,未成熟的新生儿肺需要作为气体交换器工作。围产期炎症/感染、机械通气和氧气供应加剧了肺进一步发育的条件。结果,肺发育被破坏,其特征在于肺泡化和​​(微)血管成熟以及间质变化的减少,包括纤维化组织的沉积。为了将这种形式与以前已知的情况区分开来,它被称为“新 BPD”。新 BPD 的病理生理学,特别是肺泡化停止的机制,仍未完全了解。此外,由于 BPD 的慢性性质,患有这种疾病的儿童终生受到肺部发育障碍的影响,需要治疗方法来促进极早产新生儿的宫外肺发育。目前使用不同的动物模型来模拟 BPD 的病理生理学。动物模型的可比性取决于通过最小偏差方法获得的定量数据的可用性。

因此,本研究的目的是在早产兔 BPD 高氧模型中提供第一个基于设计的肺立体学分析在妊娠第 28 天(足月前三天)通过剖宫产获得兔幼崽,并暴露于常氧 (21% O, = 8) 或高氧 (95% O, = 8) 条件。暴露7天后,进行肺功能检测,并取肺进行体视学分析。此外,还测量了肺动脉加速度和射血时间之间的比值 (PAAT/PAET)。与常氧对照相比,高氧动物的吸气能力和静态顺应性降低,而组织弹性和阻力增加。高氧动物表现出肺动脉高压的迹象,表现为 PAAT/PAET 比值降低。在高氧动物中,肺泡数量和肺泡表面积分别减少了对照值的三分之一或约 50%。然而,两组之间的平均线性截距长度和平均肺泡体积均无显着差异。高氧幼仔肺泡间隔增厚,肺泡内积聚水肿液和炎症细胞。与常氧兔相比,高氧兔的非实质血管壁增厚,血管周围空间扩大,管腔更小。

研究结果:符合人类 BPD 的病理特征。体视学数据可作为参考,将该模型与其他物种的 BPD 模型或未来的治疗干预进行比较。

本研究为 BPD 早产兔高氧模型提供了可靠的体视学参考数据。 数据证实并扩展了先前在该动物模型中的形态测量研究,并且与人类 BPD 的病理特征非常吻合。 与其常氧对应物相比,暴露于高氧的早产兔肺的特征是肺泡化减少、间隔水肿和/或纤维增生、血管壁增厚、实质功能障碍和肺动脉高压。 总之,这些发现可以作为参考,将该模型与其他物种的 BPD 模型或未来的治疗干预进行比较。

 

文章出处:

Mühlfeld C, Schulte H, Jansing JC, Casiraghi C, Ricci F, Catozzi C, Ochs M, Salomone F, Brandenberger C. Design-Based Stereology of the Lung in the Hyperoxic Preterm Rabbit Model of Bronchopulmonary Dysplasia. Oxid Med Cell Longev. 2021 Oct 6;2021:4293279. doi: 10.1155/2021/4293279. PMID: 34659632; PMCID: PMC8514964.

 

 

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Baidu
map
Baidu
map