School of Acupuncture-Moxibustion and Tuina, Beijing University of Chinese Medicine, Beijing 100029, China.
Department of Pediatrics, Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA 90502, USA.
Biomed Res Int. 2020 Jan 19;2020:3901528. doi: 10.1155/2020/3901528. eCollection 2020.
Maternal smoking and/or exposure to environmental tobacco smoke continue to be significant factors in fetal and childhood morbidity and are a serious public health issue worldwide. Nicotine passes through the placenta easily with minimal biotransformation, entering fetal circulation, where it results in many harmful effects on the developing offspring, especially on the developing respiratory system.
Recently, in a rat model, electroacupuncture (EA) at maternal acupoints ST 36 has been shown to block perinatal nicotine-induced pulmonary damage; however, the underlying mechanism and the specificity of ST 36 acupoints for this effect are unknown. Here, we tested the hypothesis that compared with EA at ST 36, EA at LU 5 acupoints, which are on lung-specific meridian, will be equally or more effective in preventing perinatal nicotine-induced pulmonary changes.
Twenty-four pregnant rat dams were randomly divided into 4 groups: saline ("S"), nicotine ("N"), nicotine + ST 36 (N + ST 36), and nicotine + LU 5 (N + LU 5) groups. Nicotine (1 mg/kg, subcutaneously) and EA (at ST 36 or LU 5 acupoints, bilaterally) were administered from embryonic day 6 to postnatal day 21 once daily. The "S" group was injected saline. As needed, using ELISA, western analysis, q-RT-PCR, lung histopathology, maternal and offspring hypothalamic pituitary adrenal axes, offspring key lung developmental markers, and lung morphometry were determined.
With nicotine exposure, alveolar count decreased, but mean linear intercept and septal thickness increased. It also led to a decrease in pulmonary function and PPAR and an increase of -catenin and glucocorticoid receptor expression in lung tissue and corticosterone in the serum of offspring rats. Electroacupuncture at ST 36 normalized all of these changes, whereas EA at LU 5 had no obvious effect.
Electroacupuncture applied to ST 36 acupoints provided effective protection against perinatal nicotine-induced lung changes, whereas EA applied at LU 5 acupoints was ineffective, suggesting mechanistic specificity and HPA axis' involvement in mediating EA at ST 36 acupoints' effects in mitigating perinatal nicotine-induced pulmonary phenotype. This opens the possibility that other acupoints, besides ST 36, can have similar or even more robust beneficial effects on the developing lung against the harmful effect of perinatal nicotine exposure. The approach proposed by us is simple, cheap, quick, easy to administer, and is devoid of any significant side effects.
母体吸烟和/或暴露于环境烟草烟雾仍然是胎儿和儿童发病率的重要因素,也是全球严重的公共卫生问题。尼古丁很容易穿过胎盘,几乎没有生物转化,进入胎儿循环,在那里它对发育中的后代产生许多有害影响,特别是对发育中的呼吸系统。
最近,在大鼠模型中,母体穴位 ST36 的电针(EA)已被证明可以阻断围产期尼古丁引起的肺损伤;然而,其潜在机制和 ST36 穴位对这种作用的特异性尚不清楚。在这里,我们测试了一个假设,即与 ST36 穴位的 EA 相比,位于肺特异性经络上的 LU5 穴位的 EA 在预防围产期尼古丁引起的肺变化方面同样有效或更有效。
将 24 只孕鼠随机分为 4 组:生理盐水(“S”)、尼古丁(“N”)、尼古丁+ST36(“N+ST36”)和尼古丁+LU5(“N+LU5”)组。尼古丁(1mg/kg,皮下)和 EA(双侧 ST36 或 LU5 穴位)从胚胎第 6 天到产后第 21 天每天给药一次。“S”组注射生理盐水。根据需要,通过 ELISA、western 分析、q-RT-PCR、肺组织病理学、母代和子代下丘脑-垂体-肾上腺轴、子代关键肺发育标志物和肺形态计量学来确定。
暴露于尼古丁后,肺泡计数减少,但平均线性截距和间隔厚度增加。它还导致肺功能和 PPAR 下降,以及肺组织中-β-连环蛋白和糖皮质激素受体表达增加和子代大鼠血清中皮质酮增加。ST36 穴位的 EA 使所有这些变化正常化,而 LU5 穴位的 EA 则没有明显效果。
ST36 穴位的 EA 提供了针对围产期尼古丁引起的肺变化的有效保护,而 LU5 穴位的 EA 则无效,这表明机制特异性和 HPA 轴参与介导 ST36 穴位的 EA 对减轻围产期尼古丁引起的肺表型的影响。这为除 ST36 以外的其他穴位对发育中肺部免受围产期尼古丁暴露的有害影响可能具有类似甚至更强的有益作用提供了可能性。我们提出的方法简单、廉价、快速、易于管理,并且没有任何明显的副作用。