参芪解郁方对母婴分离产后抑郁大鼠磁共振波谱的干预作用研究

Study on the Intervention Effect of Shen-Qi-Jie-Yu-Fang(SJ Fang)on Changes of Magnetic Resonance Spectroscopy in Rats with Maternal and Infant Separation Post-partum Depression

目的通过应用磁共振波谱(magnetic resonance spectroscopy,MRS)观察母婴分离产后抑郁大鼠脑组织内代谢物的浓度,探索参芪解郁方对母婴分离产后抑郁大鼠模型的干预作用。方法SD孕鼠72只,孕16 d,随机分为正常组、模型组、参芪解郁方组、盐酸氟西汀组,共4组,每组18只,模型组、参芪解郁方组、盐酸氟西汀组,采用母婴分离法制备产后抑郁大鼠模型,在产后1~21 d每日分离4 h。造模结束后,分别给予双蒸水、参芪解郁方、盐酸氟西汀灌胃,正常组给予等容双蒸水灌胃,再设1、2、4周3个时点,分别对大鼠进行行为学测试,并于第4周采用MRS定量检测技术扫描各组大鼠双侧海马、前额叶皮质的N-乙酰天冬氨酸(N-acety1 aspartate,NAA)、含胆碱化合物(choline,Cho)、肌醇(myo-inositol,mI)、肌酸(creatine,Cr)以及谷氨酸(glutamate,Glu),测定NAA、Cho、G1u及mI相对浓度变化,计算NAA/Cr、Cho/Cr、Glu/Cr及mI/Cr的比值。结果行为学结果:与正常组相比,模型组大鼠各时点的不动时间均明显增加(P<0.01),挣扎时间、游泳时间、旷场实验总分、蔗糖水消耗、进入开放臂的次数比例(OE/TE)和进入开放臂的时间比例(OT/TT)明显降低(P<0.01);与模型组相比,参芪解郁方组、盐酸氟西汀组大鼠各时点的不动时间明显减少(P<0.01);挣扎时间、游泳时间、旷场实验总分、蔗糖水消耗、OE/TE和OT/TT明显升高(P<0.01)。MRS结果:与正常组相比,模型组大鼠双侧前额叶皮质、海马的NAA/Cr、Cho/Cr明显降低(P<0.01),Glu/Cr明显升高(P<0.01);与模型组相比,参芪解郁方组、盐酸氟西汀组大鼠双侧海马NAA/Cr、Cho/Cr值显著升高(P<0.01)。结论参芪解郁方可以调节母婴分离PPD模型大鼠的抑郁样行为,修复PPD受损神经元,促进神经重塑,调节谷氨酸能系统及膜磷脂代谢,从而对PPD发挥治疗作用。

Objective To observe brain metabolites changes in rats with maternal and infant separation post-partum depression(PPD)and effects of Shen-Qi-Jie-Yu-Fang(SJ Fang)on maternal and infant separated PPD rat model by magnetic resonance spectroscopy(MRS).Methods 72 pregnant SD rats on the 16^(th) day of pregnancy were randomly divided into four group,normal group,model group,SJ Fang group and fluoxetine group,and with 18 rats in each group.Model group,fluoxetine group,and SJ Fang group were created in SD rats by suffered with maternal infant separation stress(MISS).They were separated daily for 4 hours from 1 to 21 day postpartum.After the modeling,rats were given intragastric administration with SJ Fang,fluoxetine and distilled water,normal group was given equal volume double distilled water.Behavioral tests were conducted at 3 time points at 1^(st),2^(nd),4^(th) week,respectively.At the 4^(th) week,the N-acety1 aspartate(NAA),choline(Cho),myo-inositol(mI),creatine(Cr)and glutamate(Glu)in the bilateral hippocampus and prefrontal cortex of rats in each group were scanned by MRS quantitative detection technology.Changes in the relative concentrations of NAA,Cho,G1u and mI were determined,and the ratios of NAA/Cr,Cho/Cr,Glu/Cr and mI/Cr were calculated.Results Behavioral results:compared with the normal group,the immobility time of model group was significantly increased at each time point(P<0.01),while the struggle time,swimming time,total score of open field experiment,sucrose water consumption,the proportion of times entering the open arm(OE/TE)and the proportion of open entries/total entries(OT/TT)were significantly decreased(P<0.01);compared with model group,both fluoxetine group and SJ Fang group decreased immobility time(P<0.01),increased swimming time,struggling time,sucrose consumption,OT/TT and OE/TE(P<0.01).MRS results:compared with normal group,NAA/Cr,Cho/Cr in bilateral prefrontal cortex and hippocampus of model group were significantly decreased(P<0.01),and Glu/Cr was significantly increased(P<0.01);compared with model group,the values of NAA/Cr and Cho/Cr in bilateral hippocampus of rats in SJ Fang group and fluoxetine group were significantly increased(P<0.01).Conclusion SJ Fang could regulate the depression-like behavior of maternal and infant separation PPD model rats,repair PPD damaged neurons,and promote neural remodeling,regulate glutamatergic system and membrane phospholipid metabolism,and thus play a therapeutic role in PPD.