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山东中医药大学针灸研究院,济南 250355
巩丽,山东中医药大学硕士研究生。E-mail:2188919240@qq.com
✉夏宇岑,副教授。E-mail:xiayucen@sdutcm.edu.cn
收稿:2024-10-15,
网络首发:2025-10-11,
纸质出版:2025-12-12
移动端阅览
巩丽, 吕凤于, 吴珍珍, 等. 孕期电针与经皮穴位电刺激对感染诱导的母婴免疫激活及后代神经精神行为的保护作用[J]. 中国针灸, 2025,45(12):1777-1788.
GONG Li, LV Fengyu, WU Zhenzhen, et al. Protective effects of electroacupuncture and transcutaneous electrical acupoint stimulation during pregnancy on maternal and fetal immune activation induced by infection and neuropsychological behavior of offspring[J]. Chinese Acupuncture & Moxibustion, 2025, 45(12): 1777-1788.
巩丽, 吕凤于, 吴珍珍, 等. 孕期电针与经皮穴位电刺激对感染诱导的母婴免疫激活及后代神经精神行为的保护作用[J]. 中国针灸, 2025,45(12):1777-1788. DOI: 10.13703/j.0255-2930.20241015-k0006.
GONG Li, LV Fengyu, WU Zhenzhen, et al. Protective effects of electroacupuncture and transcutaneous electrical acupoint stimulation during pregnancy on maternal and fetal immune activation induced by infection and neuropsychological behavior of offspring[J]. Chinese Acupuncture & Moxibustion, 2025, 45(12): 1777-1788. DOI: 10.13703/j.0255-2930.20241015-k0006.
目的:
2
比较孕期电针与经皮穴位电刺激对母体免疫激活(MIA)引发的不良妊娠结局、胎儿发育缺陷及子代神经精神行为异常的保护作用。
方法:
2
将80只C57BL/6孕鼠随机分为对照组、模型组、电针组、经皮电组和假刺激组,每组16只。妊娠第12.5天通过尾静脉注射聚肌胞苷酸复制MIA模型。成模次日,电针组和经皮电组的孕鼠均取双侧“足三里”进行电针和经皮穴位电刺激干预,频率2 Hz,电流0.5 mA,持续20 min,连续6 d。记录孕鼠体质量、生育指标及子代小鼠发育指标,液相悬浮芯片技术检测孕鼠血清及子代小鼠胎脑细胞因子和趋化因子水平,流式细胞术检测孕鼠脾脏T淋巴细胞亚群及巨噬细胞分型比例,采用旷场试验、前脉冲抑制(PPI)试验、Morris水迷宫实验评估子代小鼠空间学习与记忆能力,免疫荧光法检测子代小鼠大脑前额叶皮层(mPFC)小胶质细胞计数。
结果:
2
与对照组比较,模型组孕鼠体质量降低(
P
<
0.01),每窝产仔数、活产数减少(
P
<
0.01,
P
<
0.05),死产数增加、子代小鼠存活率降低(
P
<
0.05,
P
<
0.01);与模型组比较,电针组和经皮电组孕鼠体质量升高(
P
<
0.05),每窝产仔数、活产数增加(
P
<
0.05,
P
<
0.01),死产数减少、子代小鼠存活率升高(
P
<
0.05)。与对照组比较,模型组孕鼠血清单核细胞趋化蛋白-1(MCP-1)、白细胞介素-6(IL-6)、γ干扰素(IFN-γ)水平和脾脏M1型巨噬细胞比例升高(
P
<
0.01,
P
<
0.05),脾脏M2型巨噬细胞比例降低(
P
<
0.01);子代小鼠胎脑MCP-1、IL-6水平升高(
P
<
0.05)。与模型组比较,电针组和经皮电组孕鼠血清MCP-1、IL-6、IFN-γ水平和脾脏M1型巨噬细胞比例降低(
P
<
0.01,
P
<
0.05),脾脏M2型巨噬细胞比例升高(
P
<
0.01,
P
<
0.05);子代小鼠胎脑MCP-1、IL-6水平降低(
P
<
0.05)。与对照组比较,模型组子代小鼠总活动距离、逃避潜伏期延长(
P
<
0.05,
P
<
0.01),进入中央区域次数和穿越平台次数减少、中央区域活动时间缩短(
P
<
0.05,
P
<
0.01),平均速度升高(
P
<
0.05),PPI%、目标象限游泳时间占总时间比例、目标象限游泳路程占总路程比例降低(
P
<
0.05,
P
<
0.01)。与模型组比
较,电针组和经皮电组子代小鼠总活动距离和逃避潜伏期缩短、平均速度降低、PPI%升高、穿越平台次数增多(
P
<
0.05,
P
<
0.01),目标象限游泳时间占总时间比例、目标象限游泳路程占总路程比例升高(
P
<
0.01,
P
<
0.05);电针组子代小鼠进入中央区域次数增加、中央区域活动时间延长(
P
<
0.05,
P
<
0.01),经皮电组子代小鼠中央区域活动时间延长(
P
<
0.05)。与对照组比较,模型组子代小鼠mPFC小胶质细胞计数升高(
P
<
0.05);与模型组比较,电针组和经皮电组子代小鼠mPFC小胶质细胞计数降低(
P
<
0.05)。
结论:
2
孕期电针与经皮穴位电刺激“足三里”能有效改善感染诱发的不良妊娠结局和胚胎发育异常,并通过抑制mPFC小胶质细胞的炎性激活,改善子代小鼠的神经发育缺陷和精神障碍。
Objective
2
To compare the protective effects of electroacupuncture (EA) and transcutaneous electrical acupoint stimulation (TEAS) during pregnancy on maternal immune activation (MIA)-induced adverse pregnancy outcomes
fetal developmental defects
and neuropsychological behavior abnormalities in offspring mice.
Methods
2
Eighty pregnant C57BL/6 mice were randomly divided into 5 groups: control
model
EA
TEAS
and sham-stimulation groups
16 mice in each group. MIA models were replicated on the day 12.5 of pregnancy via tail intravenous injection with polyinosinic-polycytidylic acid. On the second day of modeling success
in the EA and TEAS groups
the interventions were delivered at bilateral "Zusanli" (ST36)
with a frequency of 2 Hz
a current of 0.5 mA
and for 20 min each day in the pregnant mice; and the interventions lasted 6 days. Body mass and fertility indexes of pregnant mice
and the development indexes of offspring mice were recorded. Liquid phase suspension chip technology was used to detect the levels of cytokines and chemotactic factors in the serum of pregnant mice and and fetal brain of offspring mice. Flow cytometry was adopted to detect the proportion of the subgroups and subtypes of spleen T lymphocytes and macrophages in pregnant mice. Using the open field test
prepulse inhibition (PPI) test and Morris water maze
the spatial learning and memory were assessed in offspring mice. Immunofluorescence staining was used to detect microglial count in the medial prefrontal cortex (mPFC) in offspring mice.
Results
2
Compared with the control group
the model group showed a reduced body mass of pregnancy mice (
P
<
0.01)
smaller litter size and fewer live births (
P
<
0.01
P
<
0.05)
the increase in dead birth and the decrease in offspring survival rate (
P
<
0.05
P
<
0.01). When compared with model group
in the EA group and the TEAS group
the body mass of pregnancy mice rose (
P
<
0.05)
litter size and live births increased (
P
<
0.05
P
<
0.01)
the dead birth was reduced and the offspring survival rate higher (
P
<
0.05). In comparison with the control group
the model group showed the increase in the levels of monocyte chemotactic protein-1 (MCP-1)
interleukin-6 (IL-6)
γ-interferon (IFN-γ) in the serum of pregnant mice
and spleen M1 macrophage proportion (
P
<
0.01
P
<
0.05)
and the decrease in spleen M2 macrophages of pregnant mice (
P
<
0.01); and the increase in MCP-1 and IL-6 in fetal brain of offspring mice (
P
<
0.05). Compared with the model group
the EA group and the TEAS group showed the decrease in MCP-1
IL-6 and IFN-γ
and spleen M1 macrophage proportion (
P
<
0.01
P
<
0.05)
and the increase in spleen M2 macrophages of pregnant mice (
P
<
0.01
P
<
0.05) ; and the decrease in MCP-1 and IL-6 in fetal brain of offspring mice (
P
<
0.05). Compared with the control group
in the model group
the total movement distance
escape incubation were extended (
P
<
0.05
P
<
0.01)
the frequency of entering the central area and crossing the platform
decreased
and the activity duration in central area was shortened (
P
<
0.05
P
<
0.01)
the average speed rose (
P
<
0.05)
PPI%
the percentage of target quadrant swimming time in the total time and that of target quadrant swimming distance in the total distance were reduced (
P
<
0.05
P
<
0.01) in offspring mice. When compared with the model group
in the EA group and TEAS group
the total movement distance and escape incubation were shortened
the average speed was reduced (
P
<
0.05)
PPI% and the frequency of crossing the platform increased (
P
<
0.05
P
<
0.01); the percentage of target quadrant swimming time in the total time and that of target quadrant swimming distance in the total distance rose (
P
<
0.05
P
<
0.01) in the offspring mice. In the EA group
the frequency of entering the central area and the activity duration in central area were higher (
P
<
0.05
P
<
0.01); and in the the TEAS group
the activity duration in central area were longer (
P
<
0.05). When compared with the control group
in the model group
microglial count in mPFC was elevated in offspring mice (
P
<
0.05). In comparison with the model group
the EA group and the TEAS group showed the decrease of microglial count in mPFC (
P
<
0.05).
Conclusion
2
EA and TEAS at "Zusanli" (ST36) during pregnancy effectively improve in the pregnancy outcomes and fetal brain developmental abnormalities induced by infection
and attenuate neurodevelopmental defects and mental disorders of offspring mice through inhibiting inflammatory activation of microglia in mPFC.
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