Comparison of Survival of Preterm Newborn Rabbits at 25-28 Days of Gestation with Perinatal Therapies at Birth Transition.
Comparison of Survival of Preterm Newborn Rabbits at 25-28 Days of Gestation with Perinatal Therapies at Birth Transition.
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DOI：
10.1152/japplphysiol.00027.2021
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发表时间：
2021-05
影响因子：
3.3
通讯作者：
Siwei Luo;Xiaojing Guo;Yaling Xu;Ying Dong;V. Rehan;B. Sun
中科院分区：
文献类型：
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作者：
Siwei Luo;Xiaojing Guo;Yaling Xu;Ying Dong;V. Rehan;B. Sun
背景
通气早产兔模型用于研究出生过渡时极度肺不成熟的适用性尚不明确。通过将该模型扩展到胎儿肺发育的早期囊泡阶段，我们评估了当代围产期疗法在存活、肺成熟方面的效果以及潜在机制。
方法
怀孕的新西兰白兔在妊娠25 - 28天分娩前48小时和24小时分别给予地塞米松（DEX）或假注射作为对照（NDEX）。出生时，新生兔被麻醉并随机分为四组，DEX组和NDEX组均分别接受表面活性物质或不接受表面活性物质，并在低潮气量下进行机械通气。
结果
在妊娠25 - 28天，维持存活率≥50%的时间范围分别为59 - 136分钟、138 - 259分钟、173 - 288分钟和437至>600分钟，这四个时间范围分别对应四组。在妊娠25 - 26天，DEX和/或表面活性物质对存活的益处更为明显，表现为肺力学改善、肺损伤评分降低、肺表面活性物质磷脂池和表面活性物质蛋白mRNA表达升高，其中DEX - 表面活性物质联合使用对结果最为有利。相比之下，妊娠27 - 28天的兔子对治疗有不同但有意义的反应。Cox回归分析显示，妊娠年龄、DEX和表面活性物质是独立的保护因素，而气胸是一个危险因素。
结论
妊娠25 - 26天的极早产兔对围产期治疗有显著反应，表现为存活时间延长、肺成熟和损伤减轻，并且与早产过渡相关疾病及其潜在机制的研究相关。
Background Eligibility of ventilated preterm rabbit model to investigate extreme pulmonary immaturity at birth transition is unknown. By extending this model to early saccular stage of fetal lung development, we evaluated efficacy in survival, lung maturation and underlying mechanisms of contemporary perinatal therapies. METHODS Pregnant New Zealand White rabbit does were given dexamethasone (DEX), or sham injection as control (NDEX), 48 and 24 h before delivery at gestational age (GA) of 25-28 days. At birth, newborn rabbits were anesthetized and randomly allocated to four groups receiving either surfactant or non-surfactant for both DEX and NDEX, and mechanically ventilated within low tidal volumes. RESULTS Ranges of time to maintain survival rate ≥ 50% in GA 25-28 days were 59-136, 138-259, 173-288, and 437 to >600 min, respectively, each across the four groups. The benefits of DEX and/or surfactant for survival were more obvious in GA 25-26 days, as judged by improved lung mechanics, lower lung injury scores, higher lung surfactant phospholipid pools and surfactant protein mRNA expression, with DEX-surfactant combination being the most optimal for the outcome. In contrast, those of GA 27-28 days had variable but meaningful responses to the treatment. Cox regression analysis revealed GA, DEX and surfactant being independently protective factors while pneumothorax a risk factor. CONCLUSION The extremely preterm rabbits at GA 25-26 days markedly responded to the perinatal therapies for longer survival, lung maturation and injury alleviation, and were relevant for study of preterm birth transition-associated morbidities and underlying mechanisms.