目的 通过磁共振波谱(MRS)观察母婴分离子代大鼠成年后Papez环路海马和前额叶皮质内代谢物水平，探讨参芪解郁方对其抑郁、焦虑样行为的作用及机制。方法 将24只孕16 d SD大鼠按照随机数字表法分为正常组、模型组、参芪解郁方组、盐酸氟西汀组，每组6只。仔鼠出生后第1～21天每天进行4 h母婴分离。从第15天开始，给母鼠灌胃相应药物，每天1次，连续7 d(参芪解郁方组:12。5g/kg，盐酸氟西汀组:2。33 mg/kg)，灌胃期间正常哺乳。第22天，仔鼠断乳，按母鼠的实验分组，将每只母鼠分娩的子代仔鼠按照随机数字表法，选取雌雄各1只，每组6只，组成正常雌鼠组、模型雌鼠组、参芪解郁方雌鼠组、盐酸氟西汀雌鼠组、正常雄鼠组、模型雄鼠组、参芪解郁方雄鼠组、盐酸氟西汀雄鼠组。饲养8周后，各组子代大鼠分别进行强迫游泳实验、蔗糖水消耗实验、旷场实验和高架十字迷宫实验，采用MRS检测海马和前额叶皮质N-乙酰天[门]冬氨酸(NAA)、胆碱化合物(Cho)、谷氨酸(Glu)、肌醇(mI)和肌酸(Cr)的相对值。结果 与正常雌鼠和雄鼠组比较，模型雌鼠和雄鼠组体质量降低，蔗糖水消耗量、旷场实验水平得分和垂直得分减少，强迫游泳不动时间增加，双侧海马和前额叶皮质NAA/Cr、Glu/Cr值下降(均P＜0。01);模型雌鼠组高架十字迷宫进入开放臂次数比例和开放臂停留时间比例减少，右侧海马的Cho/Cr值升高(P＜0。05)。与模型雌鼠和雄鼠组比较，参芪解郁方、盐酸氟西汀雌鼠和雄鼠组体质量增加，强迫游泳不动时间减少，蔗糖水消耗量、旷场实验水平得分和垂直得分增加(P＜0。01);参芪解郁方和盐酸氟西汀雌鼠组高架十字迷宫进入开放臂次数比例和开放臂停留时间比例较模型雌鼠组增加(P＜0。01)。与模型雌鼠组比较，参芪解郁方和盐酸氟西汀雌鼠组双侧海马和前额叶皮质的NAA/Cr、Glu/Cr值升高(P＜0。05);参芪解郁方和盐酸氟西汀雄鼠组右侧海马、双侧前额叶皮质的NAA/Cr值和双侧海马、右侧前额叶皮质的Glu/Cr值较模型雄鼠组升高(P＜0。05);参芪解郁方、盐酸氟西汀雌鼠和雄鼠组右侧海马的Cho/Cr值降低(P＜0。05)。结论 生命早期，母婴分离可致子代成年后出现抑郁、焦虑样行为，参芪解郁方可能通过调节Papez环路相关脑区代谢物水平发挥抗抑郁、焦虑作用。
Effect of Shenqi Jieyu Formula on magnetic resonance spectroscopy of Papez circuit-related brain regions in adult offspring of maternal separation rats
Objective To explore the effect and mechanism of Shenqi Jieyu Formula(SQJYF)on depression and anxiety-like behavior in adult offspring rats after maternal separation(MS).This was done by observing the levels of metabolites in the hippocampus and prefrontal cortex of the Papez circuit through magnetic resonance spectroscopy(MRS).Methods Twenty-four Sprague-Dawley rats at 16 days of pregnancy were divided into the normal,model,SQJYF,and fluoxetine groups using the random number table method,with six rats per group.MS was performed 4 h a day from the first to the 21st day afterbirth.Starting from the 15th day,the corresponding medications(SQJYF group:12.5 g/kg,fluxetine group:2.33 mg/kg)were administered to mother rats once a day for 7 consecutive days.Normal breastfeeding was performed during the gavage.The offspring rats were weaned on the 22nd day.According to the experimental grouping of mother rats,one male and one female offspring rat of each mother rat were randomly selected using the random number table method,with six rats per group.They were divided into normal,model,SQJYF,and fluoxetine female and male rat groups,respectively.After 8 weeks of feeding,the offspring rats in each group were subjected to forced swimming test(FST),the sucrose water consumption test,and open field tests(OFT),and the elevated plus maze(EPM)test was conducted.The relative values of N-acetyl-aspartate(NAA),choline(Cho),glutamic acid(Glu),myo-inositol(mI),and creatine(Cr)in the hippocampus and prefrontal cortex were detected using MRS.Results Compared with that of the normal female and male rat groups,the weight of the rats in the model group was decreased as well as sucrose water consumption and the horizontal and vertical scores of OFT,whereas the immobility time of FST increased.Compared with the normal female and male rat group,the NAA/Cr and Glu/Cr values in the bilateral hippocampus and prefrontal cortex of the female and male rats in the model group decreased(all P＜0.01).The proportion of rats entering the open arm and open arm residence time of the model female rat group in the EPM test decreased,whereas the Cho/Cr value of the right hippocampus of the female rats in the model group increased(P＜0.05).Compared with the model female and male rat group,the weight of the rats in the SQJYF and fluoxetine groups increased,the immobility time of FST decreased,but the sucrose water consumption and the horizontal and vertical OFT scores increased(P＜0.01).The proportion of rats entering the open arm and open arm residence time in the EPM increased in the SQJYF and fluoxetine female rat groups compared to those of the model female rat group(P＜0.01).Compared with the model female rat group,the NAA/Cr and Glu/Cr values in the bilateral hippocampus and prefrontal cortex of female rats in the SQJYF and fluoxetine groups increased.The NAA/Cr and Glu/Cr values in the right hippocampus and prefrontal cortex of male rats in the SQJYF and fluoxetine groups were higher than those in the model group(P＜0.05),whereas the Cho/Cr value in the right hippocampus of female and male rats in the SQJYF and fluoxetine groups decreased(P＜0.05).Conclusion MS in early life can lead to depression and anxiety-like behavior in adult offspring.However,SQJYF may exert antidepressant and anti-anxiety effects by regulating the metabolite levels in related brain regions of the Papez circuit.
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