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Nebulized curcumin protects neonatal lungs from antenatal insult in rats
American Journal of Physiology-Lung Cellular and Molecular Physiology ( IF 4.9 ) Pub Date : 2021-06-23 , DOI: 10.1152/ajplung.00195.2021 Cyril Guillier 1, 2, 3 , Diane Carrière 1, 2, 3 , Julien Pansiot 1, 4 , Arielle Maroni 1, 3 , Elodie Billion 1, 2, 3 , Maud Ringot 1, 4 , Jean-François Benoist 5 , Sébastien Jacques 6 , Boris Matrot 1, 4 , Pierre-Henri Jarreau 2, 3, 7, 8 , Daniel Vaiman 9 , Olivier Baud 1, 4, 10, 11 , Elodie Zana-Taïeb 1, 2, 7
American Journal of Physiology-Lung Cellular and Molecular Physiology ( IF 4.9 ) Pub Date : 2021-06-23 , DOI: 10.1152/ajplung.00195.2021 Cyril Guillier 1, 2, 3 , Diane Carrière 1, 2, 3 , Julien Pansiot 1, 4 , Arielle Maroni 1, 3 , Elodie Billion 1, 2, 3 , Maud Ringot 1, 4 , Jean-François Benoist 5 , Sébastien Jacques 6 , Boris Matrot 1, 4 , Pierre-Henri Jarreau 2, 3, 7, 8 , Daniel Vaiman 9 , Olivier Baud 1, 4, 10, 11 , Elodie Zana-Taïeb 1, 2, 7
Affiliation
Rationale: Intrauterine growth restriction (IUGR) increases the risk of bronchopulmonary dysplasia (BPD), one of the major complications of prematurity. Antenatal low-protein diet (LPD) exposure in rats induces IUGR and mimics BPD-related alveolarization disorders. Proliferator-activated receptor (PPARg) plays a key role in normal lung development and was found deregulated following LPD exposure. Objectives: Investigate the effects of nebulized curcumin, a natural PPARg agonist, to prevent IUGR-related abnormal lung development. Methods: We studied rat pups antenatally exposed to an LPD or control diet (CTL) and treated with nebulized curcumin (50 mg/kg) or vehicle from postnatal (P) days 1 to 5. The primary readouts were lung morphometric analyses at P21. Immunohistochemistry (P21) and microarrays (P6 and P11) were compared within animals exposed to LPD versus controls, with and without curcumin treatment. Results: Quantitative morphometric analyses revealed that LPD induced abnormal alveolarization as evidenced by a significant increase in Mean Linear Intercept (MLI) observed in P21 LPD-exposed animals. Early curcumin treatment prevented this effect and two-way ANOVA analysis demonstrated significant interaction between diet and curcumin both for MLI (F(1,39)=12.67,p=0.001) and Radial Alveolar Count at P21 (F(1,40)= 6.065, p=0.0182). Immunohistochemistry for FABP4, a major regulator of PPARg pathway showed a decreased FABP4+ alveolar cell density in LPD-exposed animals treated by curcumin. Transcriptomic analysis showed that early curcumin significantly prevented the activation of pro-fibrotic pathways observed at P11 in LPD-exposed animals. Conclusion: Nebulized curcumin appears to be a promising strategy to prevent alveolarization disorders in IUGR rat pups, targeting pathways involved in lung development.
中文翻译:
雾化姜黄素保护新生儿肺免受大鼠产前损伤
理由:宫内生长受限 (IUGR) 会增加支气管肺发育不良 (BPD) 的风险,这是早产的主要并发症之一。大鼠产前低蛋白饮食 (LPD) 暴露诱导 IUGR 并模拟 BPD 相关的肺泡形成障碍。增殖物激活受体 (PPARg) 在正常肺发育中起着关键作用,并且在 LPD 暴露后被发现失调。目的:研究雾化姜黄素(一种天然 PPARg 激动剂)对预防 IUGR 相关异常肺发育的影响。方法:我们研究了产前暴露于 LPD 或对照饮食 (CTL) 并在出生后 (P) 1 至 5 天用雾化姜黄素 (50 mg/kg) 或载体治疗的幼鼠。主要读数是 P21 时的肺形态计量分析。免疫组织化学 (P21) 和微阵列 (P6 和 P11) 在暴露于 LPD 的动物与对照中进行了比较,有和没有姜黄素治疗。结果:定量形态计量分析表明,LPD 诱导了异常肺泡化,正如在 P21 LPD 暴露动物中观察到的平均线性截距 (MLI) 显着增加所证明的那样。早期姜黄素治疗阻止了这种效应,双向方差分析表明饮食和姜黄素之间存在显着的相互作用,对于 MLI(F(1,39) =12.67,p=0.001) 和 P21 处的径向肺泡计数 (F ( 1,40 ) = 6.065, p=0.0182)。FABP4(PPARg 通路的主要调节因子)的免疫组织化学显示,在接受姜黄素治疗的 LPD 暴露动物中,FABP4 +肺泡细胞密度降低。转录组学分析表明,早期姜黄素显着阻止了在 LPD 暴露动物中 P11 观察到的促纤维化途径的激活。结论:雾化姜黄素似乎是预防 IUGR 大鼠幼崽肺泡形成障碍的一种有前景的策略,靶向参与肺发育的途径。
更新日期:2021-06-24
中文翻译:
雾化姜黄素保护新生儿肺免受大鼠产前损伤
理由:宫内生长受限 (IUGR) 会增加支气管肺发育不良 (BPD) 的风险,这是早产的主要并发症之一。大鼠产前低蛋白饮食 (LPD) 暴露诱导 IUGR 并模拟 BPD 相关的肺泡形成障碍。增殖物激活受体 (PPARg) 在正常肺发育中起着关键作用,并且在 LPD 暴露后被发现失调。目的:研究雾化姜黄素(一种天然 PPARg 激动剂)对预防 IUGR 相关异常肺发育的影响。方法:我们研究了产前暴露于 LPD 或对照饮食 (CTL) 并在出生后 (P) 1 至 5 天用雾化姜黄素 (50 mg/kg) 或载体治疗的幼鼠。主要读数是 P21 时的肺形态计量分析。免疫组织化学 (P21) 和微阵列 (P6 和 P11) 在暴露于 LPD 的动物与对照中进行了比较,有和没有姜黄素治疗。结果:定量形态计量分析表明,LPD 诱导了异常肺泡化,正如在 P21 LPD 暴露动物中观察到的平均线性截距 (MLI) 显着增加所证明的那样。早期姜黄素治疗阻止了这种效应,双向方差分析表明饮食和姜黄素之间存在显着的相互作用,对于 MLI(F(1,39) =12.67,p=0.001) 和 P21 处的径向肺泡计数 (F ( 1,40 ) = 6.065, p=0.0182)。FABP4(PPARg 通路的主要调节因子)的免疫组织化学显示,在接受姜黄素治疗的 LPD 暴露动物中,FABP4 +肺泡细胞密度降低。转录组学分析表明,早期姜黄素显着阻止了在 LPD 暴露动物中 P11 观察到的促纤维化途径的激活。结论:雾化姜黄素似乎是预防 IUGR 大鼠幼崽肺泡形成障碍的一种有前景的策略,靶向参与肺发育的途径。