Antenatal Saireito (TJ-114) Can Improve Pulmonary Hypoplasia and Pulmonary Vascular Remodeling in Nitrofen-Induced Congenital Diaphragmatic Hernia
Antenatal Saireito (TJ-114) Can Improve Pulmonary Hypoplasia and Pulmonary Vascular Remodeling in Nitrofen-Induced Congenital Diaphragmatic Hernia
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DOI：
10.1002/ptr.5645
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发表时间：
2016-09-01
影响因子：
7.2
通讯作者：
Kikkawa, Fumitaka
中科院分区：
文献类型：
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作者：
Hirako, Shima;Tsuda, Hiroyuki;Kikkawa, Fumitaka
先天性膈疝（CDH）可引起肺发育不全和肺动脉高压，死亡率高。本研究的目的是研究日本传统中草药产前白喉藤（TJ-114）对大鼠CDH模型的疗效和安全性。在sd - dawley大鼠胚胎第9天（E9）暴露于除草剂（硝基芬，100 mg）以诱导CDH，并在E10 ~ E20期间口服赛雷托（2000 mg/kg/d）。在E21，胎儿出生了。产前Saireito显著降低CDH发生率（p < 0.01），增加肺体积（p < 0.01），组织学分析改善肺泡化和肺动脉重塑，气相分析改善呼吸功能（pH, p < 0.05, PCO2, p < 0.01）。此外，产前Saireito显著降低了肺动脉内皮素-1和内皮素受体A的表达。综上所述，我们的研究结果表明，产前Saireito可以改善胎儿肺发育不全和肺血管重塑，从而改善大鼠CDH模型的呼吸功能。版权所有：John Wiley & Sons， Ltd。
Congenital diaphragmatic hernia (CDH) can induce lung hypoplasia and pulmonary hypertension and is associated with high mortality. The purpose of this study is to examine the efficacy and safety of antenatal Saireito (TJ-114), a traditional Japanese herbal medicine, in a rat CDH model. Sprague-Dawley rats were exposed to an herbicide (nitrofen, 100 mg) on embryonic day 9 (E9) to induce CDH, and antenatal Saireito (2000 mg/kg/day) was orally administered from E10 to E20. On E21, fetuses were delivered. Antenatal Saireito significantly decreased the incidence of CDH (p < 0.01), increased lung volume (p < 0.01), improved alveolarization and pulmonary artery remodeling using histological analysis, and improved respiratory function using gasometric analysis (pH; p < 0.05, and PCO2; p < 0.01). In addition, antenatal Saireito significantly decreased endothelin-1 and endothelin receptor A expression in the pulmonary arteries. Taken together, our results demonstrated that antenatal Saireito can improve fetal pulmonary hypoplasia and pulmonary vascular remodeling and, as a result, can improve respiratory function in a rat CDH model. Copyright (C) 2016 John Wiley & Sons, Ltd.