Frontier Molecular Medical Research Center in Children, Changhua Christian Children Hospital, Changhua County, Taiwan.
Department of Pathology, Changhua Christian Hospital, Changhua, Taiwan.
PLoS One. 2023 May 18;18(5):e0285944. doi: 10.1371/journal.pone.0285944. eCollection 2023.
Hyperoxia plays a significant role in the pathogenesis of lung injury, such as bronchopulmonary dysplasia (BPD), in premature infants or newborns. BPD management aims to minimize further injury, provide an optimal environment to support growth and recovery. In clinic neonatal care, we need a new therapy for BPD. Heat shock protein 70 (Hsp70) inhibit cell apoptosis and promote cell repair allowing cells to survive lethal injury. We hypothesized that Hsp70 could be used to prevent hyperoxia related BPD in the neonatal rat model through its anti-apoptotic and anti-inflammatory effects. In this study, we explored the effect of Hsp70 on hyperoxia-induced lung injury using neonatal rats. Neonatal Wistar rats were delivered naturally at full term of gestation and were then pooled and randomly assigned to several groups to receive heat stimulation (41°C for 20 min) or room temperature conditions. The Hsp70 group received recombinant Hsp70 intraperitoneally (200 μg/kg, daily). All newborn rats were placed under hyperoxic conditions (85% oxygen) for 21 days. Survival rates in both heat-hyperoxia and Hsp70-hyperoxia groups were higher than those in the hyperoxia group (p < 0.05). Both endogenous and exogenous Hsp70 could reduce early apoptosis of alveolar cells under hyperoxia. Additionally, there were less macrophage infiltration in the lung of the Hsp70 groups (p < 0.05). Heat stress, heat shock proteins, and exogenous recombinant Hsp70 significantly increased the survival rate and reduced pathological hyperoxia induced lung injuries in the development of BPD. These results suggest that treating hyperoxia-induced lung injury with Hsp70 may reduce the risk of developing BPD.
高氧在早产儿或新生儿的肺损伤发病机制中起重要作用，例如支气管肺发育不良（BPD）。BPD 的管理旨在尽量减少进一步的损伤，提供一个最佳的环境来支持生长和恢复。在新生儿临床护理中，我们需要一种新的 BPD 治疗方法。热休克蛋白 70（Hsp70）抑制细胞凋亡并促进细胞修复，使细胞能够耐受致死性损伤。我们假设 Hsp70 可以通过其抗凋亡和抗炎作用，用于预防新生大鼠模型中的高氧相关 BPD。在这项研究中，我们使用新生大鼠探索了 Hsp70 对高氧诱导的肺损伤的影响。新生 Wistar 大鼠在足月时自然分娩，然后汇集并随机分配到几个组中，接受热刺激（41°C 20 分钟）或室温条件。Hsp70 组接受重组 Hsp70 腹腔内注射（200μg/kg，每日）。所有新生大鼠均置于高氧环境（85%氧气）中 21 天。热-高氧组和 Hsp70-高氧组的存活率均高于高氧组（p<0.05）。内源性和外源性 Hsp70 均可减少高氧下肺泡细胞的早期凋亡。此外，Hsp70 组的肺巨噬细胞浸润较少（p<0.05）。热应激、热休克蛋白和外源性重组 Hsp70 显著提高了 BPD 发展过程中存活率并减轻了高氧诱导的肺损伤的病理性。这些结果表明，用 Hsp70 治疗高氧诱导的肺损伤可能降低发生 BPD 的风险。
