| ObjectiveElectroacupuncture on the normal group of immunomodulation and anti-inflammatory action has been widely reported,while the immune regulation and anti-inflammatory action of pregnancy rarely reported.At the same time,electroacupuncture on the maternal immune activation induced mental disorders during pregnancy at home and abroad have not been reported,and the safety of electroacupuncture treatment is still controversial.This study was carried out by electroacupuncture at the time of immunization activating the mouse Zusanli(ST36)during pregnancy,aim at:1)To verify the safety of electroacupuncture treats infection/immune activation during pregnancy.2)To observe the immunomodulation and anti-inflammatory action of electroacupuncture on pregnant mice.3)To investigate the effect and mechanism of electroacupuncture intervention on maternal immune activation induced progeny schizophrenia during pregnancy.Method1.The Poly I:C model during pregnancy and electroacupuncture treatment Twenty four wild type C57BL/6 mice during second trimester of pregnancy(GD12.5)were randomly divided into three groups:control group,model group and electroacupuncture group.There were eight mice in each group.The model group and electroacupuncture group mice were injected Poly I:C by cauda vein in order to induce immune activation.The other mice in control group were injected with the same amount of saline by the same method.After the next day,electroacupuncture group was given the treatment of bilateral ST36 for 7 days until delivery,and the non-electroacupuncture groups were not treated.But the rest was consistent with the electroacupuncture group.2.Detection of peripheral inflammation environment and immune activation conditions in pregnant miceThe expression levels of IL-1?,IL-6 and TNF-? in peripheral blood of pregnant mice were tested by enzyme-linked immunosorbent assay(ELISA).After electroacupuncture treatment for one week,the expression levels of inflammatory factors in peripheral blood of pregnant mice tested by ELISA.3.Physiological Index of pregnant mice and Developmental Index of progeny MiceThe changes of body weight were observed and recorded before and after birth,and the results of delivery were recorded and analyzed.The pogeny of pregnant mice,the survival of offspring and the development indexes of offspring were analyzed and analyzed.4.Evaluation of Mental State and Cognitive Function Index in Adolescent MiceThe offspring mice were tested for the following behavioral criteria at 8 weeks of age:Locomotor activity,Pre-Pulse Inhibitation,3-Chambered Social Test and Morris water maze.Results1.The inflammatory index(IL-1?,IL-6 and TNF-?)The level of IL-6 in electroacupuncture group was significantly lower than that in model group after seven days treatment,but the difference between electroacupuncture group and control group was not statistically significant.The level of IL-6 in model group was significantly higher than that of the control group.The difference between IL-1? and TNF-? were not statistically significant.2.Developmental IndexThe difference on the weight of pregnant mice between the three groups were not statistically significant.The difference on the weight of offspring in the day of 21 was statistically,but there was no statistically significant in P1,P7 and P56.The mortality of P21 in the control group was 24%,56%in the model group and 17%in the electroacupuncture group.3.Behavioral IndexBehavioral indicators of open field,model group compared with control group,the total activity significantly increased,the central exploration significantly reduce the proportion of the time and distance,The curative group compared with model group,the total activity dropped significantly,the central exploration considerably increase the proportion of time and distance.In prepulse inhibition(PPI),the model group had a significantly reduced response to 75 dB and 85 dB prepulse inhibition,compared with control group.The curative group had a significantly elevated response to 75 dB and 85 dB prepulse inhibition,compared with control group.In three-chambered test,the time spent around the social cylinder with a stimulus mouse inside was significantly reduced in model group,compared with control group.The curative group and model group showed no difference in the time spent around a cylinder with a stimulus mouse inside.In the Morris water maze(MWM)experiment,each group was able to locate the submerged platforms and the latency to find the platform was no difference.In the probe trial,however,the number of times that the model group swam in the target quadrant decreased significantly,compared to control group.The number of times that the curative group swam in the target quadrant elevated significantly,compared to model group.4.Parvalbumin-positive interneurons(PV+interneurons)countingPV+interneurons was assessed by unilateral counting of hippocampus DG area with a stereology system stereo investigator,showing that there were significantly less PV+interneurons in the model group than the control group and there were significantly more PV+interneurons in the curative group than the model group.However,there were no statistically difference among the three groups in the medial prefrontal cortex(mPFC)area.ConclusionElectroacupuncture on the pregnant mice ST36 can specifically down-regulate the level of IL-6 in the immune activated during pregnancy,reduce the maternal inflammation response,increase the survival rate of the offspring mice,and can partially improve the schizophrenia symptoms and cognitive levels of offspring.This study confirmed the safety of electroacupuncture during pregnancy,the effectiveness of anti-inflammatory during pregnancy,and through the anti-inflammatory effect of electroacupuncture can be to some extent to improve the schizophrenia-like symptoms and cognitive functions of offspring,which provided the experimental basis for the early treatment of maternal immune activation and schizophrenia during the treatment of Chinese medicine. |
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