| The purposes:In this study,the model of postpartum depression rat model and the offspring of postpartum and depressed mother rats were constructed by mother infant separation,and the intervention was performed by Chinese medicine Shenqi Jieyu formula,.To observe the behavioral changes of postpartum depressed mother mice and their offspring,and evaluate the feasibility of the mother infant separation method to create an animal model of postpartum depression.Postnatally,magnetic resonance spectroscopy was used to further observe the brain tissue metabolite levels in the hippocampus and prefrontal cortex in the adult Papez circuit related brain regions of postpartum depressed mothers and their offspring,reveal the biological mechanism of postpartum depression from the perspective of neuroimaging and the effect on the offspring’s adulthood,occurrence and development of pathological changes,Elucidation to reveal the intervention effects of the traditional Chinese medicine Shenqi Jieyu formula on maternal infant separation of postpartum depressed rats and their offspring into adulthood.Methods:A total of 24 Sprague Dawley(SPF)-grade pregnant rats at 16 days of gestation were selected and randomly divided into normal,model,traditional Chinese medicine and Western Medicine groups,with six animals in each group.Pregnant mice were assigned birth as day 0 after delivery and were denoted as PND0,except for the normal group,in which maternal separation was performed daily for 4 h during lactation(PND1-PND 21).The dams were subjected to drug intervention at day 15(PND 15)with a drug gavage volume of 1 ml/100 g body weight.The traditional Chinese medicine group was administered with granules from a self mimicking shenqijieyu formula,the western medicine group was administered with fluoxetine hydrochloride capsules,and the normal and model groups were administered with isovolumetric double distilled water by gavage for 2 weeks.At the end of the gavage(PND 22)in the dams,behavioral experiments and magnetic resonance spectroscopy were performed,and levels of N-acetylaspartate(NAA),choline containing compounds(Cho),myo inositol(ml),creatine(Cr),as well as glutamic acid(Glu)were detected and analyzed in the bilateral hippocampus and bilateral prefrontal cortex of rats from each group.The postnatal pups of the four groups of rats used for mother infant separation were randomly selected from six females and six males,and consisted of a normal group of females,a model group of females,a Chinese medicine group of females,a western medicine group of males,a model group of males,a Chinese medicine group of males,and a western medicine group of males,for a total of 48 pups.All but one of the normal litters(PND1-PND21)were separated from the mother and child for 4 h each day.Pups were caged until the end of week 8(PND56)after weaning at day 22(PND22)for behavioral experiments and magnetic resonance spectroscopy.The levels of N-acetylaspartate(NAA),choline containing compounds(Cho),creatine(Cr),myo inositol(ml),as well as glutamate(Glu)in the bilateral hippocampus and bilateral prefrontal cortex of rats in each group were examined and analyzed.Results:1.Maternal behavioral results1.1 Body weightAt 1 and 2 weeks postpartum,the body weights of model group,TCM group and Western medicine group were decreased compared with normal group(P<0.01,P<0.01,P<0.01);At 3 weeks postpartum,it was decreased in the model group compared with the normal group(P<0.01)and increased in the TCM and Western medicine groups compared with the model group(P<0.01).1.2 Open field testIn the open field test,the horizontal and vertical OFT scores of the model group rats were significantly reduced compared to the normal group(P<0.01),while the traditional Chinese medicine group and the western medicine group rats were significantly increased compared to the model group(P<0.01,P<0.01),but there was a difference compared to the normal group(P<0.01,P<0.01).1.3 Sucrose water consumptionThe water consumption of sucrose in the model rats was significantly reduced compared with that in the normal group(P<0.01).Sucrose water consumption of rats in the TCM and Western medicines groups increased significantly compared with that of the model group(P<0.01,P<0.01),but was significantly different from that of the normal group(P<0.01,P<0.01).1.4 Forced swimming testFST immobility time was significantly increased(P<0.01)in the model group compared with the normal group,and significantly decreased(P<0.01,P<0.01)in the traditional Chinese medicine and Western medicine groups compared with the model group,but was higher(P<0.01,P<0.01)in the Western Medicine group.FST struggling time of the model rats significantly decreased compared to the normal group struggling time(P<0.01).Decreased in the traditional Chinese and Western medicine groups compared with the normal group(P<0.01,P<0.01).FST swimming time in the model group,the swimming time of rats in the model group was significantly decreased compared with the normal group(P<0.01).The swimming time of rats in the traditional Chinese medicine group and Western medicine group was decreased compared with the normal group(P<0.01,P<0.01).1.5 Elevated plus mazeThe proportion of the number of EPM entries into the open arm in the model rats was significantly decreased compared with that in the normal group(P<0.01).The ratio of the number of EPM entries into the open arms in the TCM and Western medicine groups was significantly increased compared with that in the model group(P<0.01,P<0.01,respectively).The proportion of the open arm dwell time in the EPM of rats in the model group was significantly reduced compared with that in the normal group(P<0.01).The proportion of EPM open arm dwell time of rats in the traditional Chinese medicine and Western medicine groups increased significantly compared with that in the model group,with statistical significance(P<0.01,P<0.01).2.Hippocampal and prefrontal cortex magnetic resonance spectroscopy results in damsThe NAA/Cr values in the left hippocampus and left prefrontal lobe of the model group were significantly lower than those in the normal group(P<0.01);The NAA/Cr values in the left hippocampus and left prefrontal cortex of female rats in the Chinese medicine group and the Western medicine group were significantly higher than those in the model group(P<0.01,P<0.01).The Glu/Cr values in the left hippocampus of female rats in the model group were significantly lower than those in the normal group(P<0.01),while the Glu/Cr values in the left hippocampus of female rats in the Chinese medicine group and the Western medicine group were significantly higher than those in the model group(P<0.01,P<0.01).The mI/Cr values in the left prefrontal cortex of female rats in the Chinese medicine group were higher than those in the model group(P<0.01).The NAA/Cr values in the right hippocampus and right prefrontal cortex of the model group were significantly reduced compared to the normal group(P<0.01);The NAA/Cr values in the right hippocampus and right prefrontal cortex of the mother rats in the Chinese medicine group and the Western medicine group were significantly higher than those in the model group(P<0.01,P<0.01).The Glu/Cr values in the right hippocampus of female rats in the model group were significantly lower than those in the normal group(P<0.01),while the Glu/Cr values in the right hippocampus of female rats in the traditional Chinese medicine group were higher than those in the model group(P<0.01).The Cho/Cr values of the right prefrontal cortex in the Western medicine group were lower than those in the model group(P<0.05).The ml/Cr values of the right prefrontal cortex in the model group were significantly lower than those in the normal group(P<0.01),while the Cho/Cr values of the right prefrontal cortex in the traditional Chinese medicine group were higher than those in the model group(P<0.01).3.Behavioural performance of maternal separation offspring in adulthood3.1 Body weightThe weight of female mice in the model group decreased at all time points compared to the normal group(P<0.01),while female mice in the traditional Chinese medicine group and the western medicine group significantly increased at all time points compared to the model group(P<0.01,P<0.01),but there was still a difference compared to the normal group female mice(P<0.01,P<0.01);The weight of male mice in the model group decreased significantly compared to the normal group at all time points(P<0.01),while male mice in the Chinese medicine group and the Western medicine group increased significantly compared to the model group(P<0.01,P<0.01).However,there was a difference between male mice in the Chinese medicine group and the normal group(P<0.01);Compared with the female mice in the model group,the male mice in the model group had a higher body weight at all time points(P<0.01)3.2 Open field textIn terms of OFT horizontal and vertical scores,compared with the normal group of female mice,the model group of female mice significantly decreased(P<0.01),while the traditional Chinese medicine and western medicine groups of female mice significantly increased compared to the model group of female mice(P<0.01,P<0.01),but there was a difference compared to the normal group of female mice(P<0.01,P<0.05);The male mice in the model group showed a significant decrease compared to the normal group(P<0.01),while the male mice in the traditional Chinese medicine and western medicine groups showed a significant increase compared to the male mice in the model group(P<0.01,P<0.01);Compared with the female mice in the model group,the OFT level score of the male mice in the model group was significantly higher(P<0.01).3.3 Sucrose water consumption experimentsIn the sucrose water consumption experiment,the consumption of females in the model group decreased significantly compared with females in the normal group(P<0.01),and increased significantly compared with females in the traditional Chinese medicine and Western medicine groups(P<0.01,P<0.01),but the consumption of females in the traditional Chinese medicine group decreased significantly compared with females in the normal group(P<0.05);The consumption of CO ff EE by males in the model group was signifcantly decreased compared with that of males in the normal group(P<0.01),and that of TCM and Western medicines was signifcantly increased compared with that of males in the model group(P<0.01,P<0.01,respectively);The water consumption of sucrose was significantly increased in males of the model group compared with females of the model group(P<0.01).3.4 Forced swimming textThe immobility time of female mice in the model group was significantly increased compared with that of female mice in the normal group(P<0.01),while that of female mice in the traditional Chinese medicine group and that of female mice in the western medicine group was significantly decreased compared with that of female mice in the model group(P<0.01,P<0.01,respectively);The immobility time of the males in the model group was significantly increased compared with that of the males in the normal group(P<0.01),that of the males in the traditional Chinese medicine and Western medicine groups was significantly increased compared with that of the males in the model group(P<0.01,P<0.01),and that of the males in the western medicine group was significantly increased compared with that of the males in the normal group(P<0.05);Compared with the female rats in the model group,the immobility time of the male rats in the model group was decreased(P<0.01).The struggling time of the females in the model group was significantly decreased compared with that of the females in the normal group(P<0.01),and increased compared with that of the females in the traditional Chinese and Western medicine groups(P<0.05,P<0.05),but was significantly different from that of the females in the normal group(P<0.01,P<0.05);Males in the model group spent significantly less time struggling compared with males in the normal group(P<0.01).3.5 Elevated plus mazeCompared with normal females,females in the model group showed a significant decrease in the proportion of times they entered the open arm(P<0.01),while females in the traditional Chinese medicine and Western medicine groups showed a significant increase in the proportion of times they entered the open arm(P<0.01;The ratio of the number of entries into the open arm was significantly decreased in the males of the model group compared with the males of the normal group(P<0.01);Compared with the females in the model group,males in the model group showed a significant increase in the proportion of times they entered the open arms(P<0.01).Compared with normal females,the ratio of open arm dwell time of females in the model group decreased significantly(P<0.01),while females in the traditional Chinese medicine and Western medicine groups increased significantly(P<0.01,P<0.01);The proportion of time spent in the open arms was significantly reduced in males of the model group compared with males of the normal group(P<0.01;The proportion of time spent in the open arms increased significantly in males of the model group compared with females of the model group(P<0.01).4.Magnetic Resonance Spectroscopy Results of Bilateral Hippocampus and prefrontal Cortex after maternal separation offspring in adulthoodThe NAA/Cr values in the bilateral hippocampus and prefrontal cortex of female mice in the model group were significantly lower than those in the normal group(P<0.01).The NAA/Cr values in the bilateral hippocampus and prefrontal cortex of female mice in the Chinese medicine group and Western medicine group were significantly higher than those in the model group(P<0.01,P<0.01).The NAA/Cr values in the bilateral hippocampus and prefrontal cortex of male mice in the model group were significantly lower than those in the normal group(P<0.01).The NAA/Cr values in the bilateral prefrontal cortex and right hippocampus of male rats in the Chinese medicine group and Western medicine group were significantly increased compared to male rats in the model group(P<0.01,P<0.01).The Glu/Cr values in the bilateral hippocampus and prefrontal cortex of female mice in the model group were significantly lower than those in the normal group(P<0.01);The Glu/Cr values in the bilateral hippocampus and prefrontal cortex of female mice in the Chinese medicine group and Western medicine group were significantly increased compared to the model group(P<0.01,P<0.05).The Glu/Cr values in the bilateral hippocampus and prefrontal cortex of male mice in the model group were significantly lower than those in the normal group(P<0.01).The Glu/Cr values in the bilateral hippocampus and right prefrontal cortex of male rats in the Chinese medicine group and Western medicine group were significantly increased compared to male rats in the model group(P<0.01,P<0.05).The Glu/Cr values in the left prefrontal cortex of male mice in the Western medicine group increased compared to male mice in the model group(P<0.05).The Cho/Cr values in the right hippocampus of female mice in the model group were higher than those in the normal group(P<0.05).The Cho/Cr values in the right hippocampus of female mice in the Chinese medicine group and Western medicine group were lower than those in the model group(P<0.05,P<0.05).The Cho/Cr values in the right hippocampus of male rats in the Chinese medicine group and the Western medicine group were lower than those in the model group(P<0.05,P<0.05).Conclusions1.The method of mother infant separation can simulate a model of postpartum depression,and in the early stages of life,mother infant separation can lead to depression like behavior in offspring as adults.2.The onset of PPD is related to metabolic abnormalities in brain regions related to the Papez circuit,and Shenqi Jieyu Formula has a certain intervention effect.3.The depressive behavior of mothers and infants in the early stages of life after ion generation and adulthood is related to metabolic abnormalities in the brain regions related to the Papez circuit.The Shenqi Jieyu Formula has a regulatory effect,is safe and effective,and does not affect lactation. |
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