Developmental Timing Determines the Protective Effect of Maternal Electroacupuncture on Perinatal Nicotine Exposure-Induced Offspring Lung Phenotype
Developmental Timing Determines the Protective Effect of Maternal Electroacupuncture on Perinatal Nicotine Exposure-Induced Offspring Lung Phenotype
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发育时机决定母亲电针对围产期尼古丁暴露诱导的后代肺表型的保护作用
DOI：
10.1155/2020/8030972
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发表时间：
2020-02-28
影响因子：
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通讯作者：
Rehan, Virender K.
中科院分区：
文献类型：
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作者：
Dai, Jian;Ji, Bo;Rehan, Virender K.
导言。发育中的后代在环境中暴露于香烟烟雾或尼古丁是许多慢性呼吸道疾病的重要诱因，如哮喘、肺气肿、肺纤维化等。研究表明，在孕期和哺乳期电针母体“足三里”穴对围产期尼古丁暴露(PNE)所致的肺损伤有保护作用。然而，达到这一效果的最有效时间段，即产前和出生后，还没有确定。目的探讨电针对苯乙醇胺(PNE)诱导的子代肺表型保护作用的最佳发育时机。方法孕鼠给予(1)生理盐水(“S”组)、(2)尼古丁(“N”组)、(3)尼古丁 + 电针(“电针前”组)、(4)尼古丁 + 电针(“电针后”组)和(5)尼古丁 + 电针(“电针前后”组)。每日1次注射尼古丁(1 mg/kg，100 μL)，在指定的时间段内每日1次在双侧丘36穴位注射电针。实验结束时，测定仔鼠和母鼠下丘脑-垂体-肾上腺(HPA)轴的关键标志物，以及子代肺功能、形态计量学和肺发育的中央分子标志物。结果尼古丁暴露后，大鼠肺泡平均线形截距增加，平均肺泡数减少，肺组织PPARγ水平降低，糖皮质激素受体(GR)和血清皮质酮(CORT)水平升高，与已知的PNE诱导的肺表型一致。尼古丁暴露组母鼠下丘脑促肾上腺皮质激素释放激素(CRH)水平降低，而垂体促肾上腺皮质激素(ACTH)和血清皮质醇水平升高。在电针前和电针后组，PNE诱导的肺形态计量学、肺发育标记物和HPA轴的改变被阻断。在“电针前”组，PNE诱导的肺形态计量学、GR和母体HPA轴的改变得到改善；肺PPARγ水平降低，而糖皮质激素受体(GR)和血清皮质酮(CORT)水平升高，与PNE诱导的肺表型一致。尼古丁暴露组母鼠下丘脑促肾上腺皮质激素释放激素(CRH)水平降低，而垂体促肾上腺皮质激素(ACTH)和血清皮质醇水平升高。在电针前和电针后组，PNE诱导的肺形态计量学、肺发育标记物和HPA轴的改变被阻断。在“Pre-EA”组，PNE诱导的肺形态计量学、GR和母体HPA轴的改变有所改善；肺PPAR。结论母体电针在出生前和出生后均可保护子代肺的结构和功能，尽管围产期暴露于尼古丁。在“产前”使用电针的效果有限，而在“出生后”使用电针则无效，这表明电针对PNE诱导的肺表型的调节作用仅限于肺发育的特定时间段。
Introduction. Environmental exposure of the developing offspring to cigarette smoke or nicotine is an important predisposing factor for many chronic respiratory conditions, such as asthma, emphysema, pulmonary fibrosis, and so forth, in the exposed offspring. Studies showed that electroacupuncture (EA) applied to maternal “Zusanli” (ST36) acupoints during pregnancy and lactation protects against perinatal nicotine exposure- (PNE-) induced lung damage. However, the most effective time period, that is, prenatal vs. postnatal, to attain this effect has not been determined. Objective To determine the most effective developmental timing of EA's protective effect against PNE-induced lung phenotype in the exposed offspring. Methods Pregnant rats were given (1) saline (“S” group); (2) nicotine (“N” group); (3) nicotine + EA, exclusively prenatally (“Pre-EA” group); (4) nicotine + EA, exclusively postnatally (“Post-EA,” group); and (5) nicotine + EA, administered both prenatally and postnatally (“Pre- and Post-EA” group). Nicotine was injected once daily (1 mg/kg, 100 μl) and EA was administered to bilateral ST36 acupoints once daily during the specified time-periods. At the end of the experimental periods, key hypothalamic pituitary adrenal (HPA) axis markers in pups and dams, and lung function, morphometry, and the central molecular markers of lung development in the offspring were determined. Results After nicotine exposure, alveolar mean linear intercept (MLI) increased, but mean alveolar number (MAN) decreased and lung PPARγ level decreased, but glucocorticoid receptor (GR) and serum corticosterone (Cort) levels increased, in line with the known PNE-induced lung phenotype. In the nicotine exposed group, maternal hypothalamic corticotropin releasing hormone (CRH) level decreased, but pituitary adrenocorticotropic hormone (ACTH) and serum Cort levels increased. In the “Pre- and Post-EA” groups, PNE-induced alterations in lung morphometry, lung development markers, and HPA axis were blocked. In the “Pre-EA” group, PNE-induced changes in lung morphometry, GR, and maternal HPA axis improved; lung PPARγ level decreased, but glucocorticoid receptor (GR) and serum corticosterone (Cort) levels increased, in line with the known PNE-induced lung phenotype. In the nicotine exposed group, maternal hypothalamic corticotropin releasing hormone (CRH) level decreased, but pituitary adrenocorticotropic hormone (ACTH) and serum Cort levels increased. In the “Pre- and Post-EA” groups, PNE-induced alterations in lung morphometry, lung development markers, and HPA axis were blocked. In the “Pre-EA” group, PNE-induced changes in lung morphometry, GR, and maternal HPA axis improved; lung PPAR Conclusions Maternal EA applied to ST36 acupoints during both pre- and postnatal periods preserves offspring lung structure and function despite perinatal exposure to nicotine. EA applied during the “prenatal period” affords only limited benefits, whereas EA applied during the “postnatal period” is ineffective, suggesting that the EA's effects in modulating PNE-induced lung phenotype are limited to specific time-periods during lung development.