Insulin-like growth factor-1 reduces hyperoxia-induced lung inflammation and oxidative stress and inhibits cell apoptosis through PERK/eIF2α/ATF4/CHOP signaling
Insulin-like growth factor-1 reduces hyperoxia-induced lung inflammation and oxidative stress and inhibits cell apoptosis through PERK/eIF2α/ATF4/CHOP signaling
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DOI：
10.1080/01902148.2022.2106388
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发表时间：
2022-07-24
影响因子：
1.7
通讯作者：
Jin, Zhengyong
中科院分区：
文献类型：
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作者：
Cui, Haixia;Zhang, Shujian;Jin, Zhengyong
背景：胰岛素样生长因子-1(IGF-1)是胰岛素家族的一员，与胰岛素高度同源，具有抗炎和抗氧化应激等特性。然而，IGF-1对高氧性肺损伤的潜在保护作用尚不清楚。本研究旨在探讨胰岛素样生长因子-1在新生大鼠高氧性肺损伤中的作用及其机制。材料和方法：苏木精-伊红染色观察肺组织病理变化，透射电子显微镜观察肺组织超微结构，酶联免疫吸附试验检测肺泡灌洗液中促炎症细胞因子水平。测定肺组织丙二醛、谷胱甘肽和超氧化物歧化酶活性。TUNEL法检测肺组织细胞凋亡，免疫印迹法检测肺组织Bax、Bcl2、Caspase 3、p-perk、p-eIF2α、ATF4、CHOP的表达。测定肺组织湿/干重比。结果：腹腔注射IGF-1可有效减轻高氧所致的肺组织损伤，减轻炎症细胞的产生和促炎细胞因子的释放，减轻氧化应激，减少细胞凋亡。此外，IGF-1下调ATF4、CHOP和Bax/Bcl2的表达，并抑制PERK和eIF2α的磷酸化。结论：IGF-1通过PERK/eIF2α/ATF4/CHOP信号通路减轻高氧诱导的新生大鼠肺炎症和氧化应激，抑制细胞凋亡。
Background: Insulin-like growth factor-1 (IGF-1), a member of the insulin family, has a high degree of homology with insulin and exhibits anti-inflammatory and anti-oxidative stress properties. However, the potential protective effect of IGF-1 on hyperoxia-induced lung injury remains unknown. In this study, we aimed to explore the effects and mechanism of action of IGF-1 in hyperoxia-induced lung injury in neonatal rats. Materials and Methods: Hematoxylin-eosin staining was used to observe pathological changes in lung tissue; transmission electron microscopy was used to examine the ultrastructure, and ELISA was used to detect the level of pro-inflammatory cytokines in bronchoalveolar lavage fluid. Further, malondialdehyde, glutathione, and superoxide dismutase activities in lung tissue were evaluated. TUNEL staining was used to detect cell apoptosis, and western blot analysis was used to detect the expression of Bax, Bcl-2, Caspase-3, p-PERK, p-eIF2 alpha, ATF4, and CHOP in the lung tissue. Moreover, the wet/dry weight ratio of lung tissue was determined. Results: Intraperitoneal injection of IGF-1 effectively reduced lung tissue damage induced by hyperoxia; production of inflammatory cells and release of pro-inflammatory cytokines, oxidative stress, and cell apoptosis. Further, IGF-1 down-regulated the expression of ATF4, CHOP, and Bax/Bcl-2, and inhibited the phosphorylation of PERK and eIF2 alpha. Conclusion: The results suggest that IGF-1 reduces hyperoxia-induced lung inflammation and oxidative stress in neonatal rats through the PERK/eIF2 alpha/ATF4/CHOP signaling pathway and inhibits cell apoptosis.