The Mechanism Of Intestinal Microecological Imbalance Inducing Depression-like Behavior In Rats And The Mechanism Of Traditional Chinese Medicine

Depression is a kind of mental and psychological disease whose main clinical manifestations are marked and persistent low mood,slow thinking,lack of interest,cognitive function and conscious activity.In recent years,due to the rapid development of society and the continuous acceleration of life rhythm,the psychological pressure on people is increasing day by day.The prevalence of depression is increasing year by year.The current global prevalence of depression has reached 8%?12%,which is seriously damaged People's physical and mental health has become the common focus of all mankind.The pathogenesis of depression is very complicated,involving neuroendocrine,immune,genetic,biochemical and psychosocial factors,including the hypothesis of monoamine transmitters,hypothalamic-pituitary-adrenal axis(HPA)axis hyperactivity theory and immune inflammation factor theory The more attention is paid to it,the occurrence and development of depression are mainly related to the abnormality of monoamine neurotransmitters in the synaptic space of the brain,the negative feedback failure of the HPA axis,and the activation of the immune system,and gradually become a research hotspot.Mitochondria are the "powerhouses" of eukaryotic cell life activities.Mitochondrial dysfunction can cause damage to cell functions and lead to low energy levels in multiple systems.This is consistent with the somatic hypokinetic symptoms of depression.More and more studies have confirmed depression Correlation with mitochondria suggests that there are abnormalities in the structure and function of mitochondria in multiple parts of the body of patients with depression.Improving mitochondrial function has a certain therapeutic effect on depression.There are many normal microbial communities in the healthy human intestine,most of which are bacteria,with a total of about 1,000 species.They maintain a mutually beneficial symbiotic relationship with the host and jointly maintain the health and physiological balance of the host.Dao microorganisms are essential to human health.In recent years,studies have found that the psychiatric symptoms associated with irritable bowel syndrome,inflammatory bowel disease,and fatigue syndrome,such as depression and anxiety,are closely related to the imbalance of intestinal microorganisms,and there is a correlation between intestinal microorganisms and the brain..In addition,the researchers found that patients with depression or animal models have significant changes in the diversity of intestinal microbiota,proving that there is a certain correlation between intestinal microflora disorder and depression,but whether intestinal microflora disorder can directly induce depression The disease is not clear,and the relationship between neuroendocrine-immune-mitochondrial network regulation and intestinal flora imbalance in the development of depression remains to be further studied.Sterile animals are new model animals that are cultivated by aseptic breeding and aseptic breeding.They do not carry any microorganisms in their bodies,and they are powerful tools for understanding the impact of intestinal microbiota on the host.This study is based on a sterile animal model,using fecal bacteria transplantation technology to transplant the intestinal microbiota of patients with severe depression and healthy people into the intestine of sterile rats,and set up a Chinese medicine group to intervene with Xingpi Jieyu Recipe to directly observe intestinal microbes The effect of swarm on rat behavior and neuroendocrine-immune-mitochondrial network and the effect of Chinese medicine interventionExperimental study 1:Research on the mechanism of intestinal microbiota on depression-like behavior in rats and the effect of Chinese medicine intervention based on neural-endocrine-immune networkObjective:To explore the effect of depressive microbiota on the behavior and neuro-endocrine-immune network of rats.Methods:8-week male sterile rats were randomly divided into blank control group,healthy transplantation group,depression transplantation group,and Chinese medicine group.The intestinal microbiota of patients with severe depression was transplanted to the depression transplantation group and the Chinese medicine group by fecal bacteria transplantation technology.In the gastrointestinal tract of bacteria rats,the intestinal microbiota of healthy people was transplanted into the gastrointestinal tract of aseptic rats in the healthy transplantation group.The sugar water preference experiment and the forced swimming experiment were carried out to evaluate the behavior of rats at the 4th weekend.Blood was collected from the orbit to separate serum,hippocampus,duodenum and skeletal muscle were collected,and neurotransmitter indicators(5-HT,DA,NE),Endocrine indicators(CORT,ACTH,CRH),immune inflammation indicators(TNF-?,IFN-?,IL-1,IL-4,IL-6,IL-10)to study intestinal microbiota on rat nerves-The influence of endocrine-immune network,reveal the microscopic mechanism of depressive microbiome-induced depression behavior,and clarify the effect mechanism of XPJY recipe.Result:1.BehaviorCompared with the blank control group and the healthy transplantation group,the sugar water preference rate in the depression transplantation group was significantly reduced,and the forced swimming immobility time was significantly prolonged;compared with the depression transplantation group,the sugar water preference rate was increased in the Chinese medicine group,and the forced swimming immobility time was reduced.2.Neurotransmitter indicators—5-HT,DA,NECompared with the blank control group and healthy transplantation group,the content of 5-HT,DA,and NE in the hippocampus of the depression transplantation group decreased significantly(P<0.01);compared with the depression transplantation group,the content of 5-HT,DA,and NE in the Chinese medicine group increased(P<0.01).3.Endocrine indicators—CORT,ACTH,CRHCompared with the blank control group and the healthy transplantation group,the serum CORT,ACTH,and CRH levels in the depression transplantation group increased significantly(P<0.01);compared with the depression transplantation group,the serum CORT,ACTH,and CRH levels decreased in the traditional Chinese medicine group(P<0.01)4.Immune indicators—TNF-?,IFN-?,IL-1,IL-4,IL-6,IL-10Compared with the blank control group and healthy transplantation group,the content of TNF-?,IFN-?,IL-6 and IL-1 in the depression transplantation group increased significantly(P<0.01),while the content of IL-4 and IL-10 decreased(P<0.01);Compared with the depression transplantation group,the content of TNF-?,IFN-?,IL-6 and IL-1 in the traditional Chinese medicine group decreased(P<0.01),and the content of IL-4 and IL-10 increased(P<0.01)Conclusion:Depressive microbiota can directly induce depressive-like behavior in sterile rats,accompanied by a significant decrease in neurotransmitter content,hyperfunction of HPA axis,and immune inflammation disorder,suggesting that depressive microbiota may induce depression-like behavior of bacterial rats,XPJY recipe has a multi-layer,multi-site,multi-target protective effect.Experimental Study 2:Based on mitochondrial energy metabolism to study the mechanism of intestinal microbiota on rat depression-like behavior and the effect of Chinese medicine interventionObjective:To analyze the mitochondrial energy metabolism characteristics,reveal the microscopic mechanism of depression-like behavior induced by the depressive microbiome,and clarify the effect mechanism of Xingpi Jieyu RecipeMethods:8-week male sterile rats were randomly divided into blank control group,healthy transplantation group,depression transplantation group,and Chinese medicine group.The intestinal microbiota of patients with severe depression was transplanted to the depression transplantation group and the Chinese medicine group by fecal bacteria transplantation technology.In the gastrointestinal tract of bacteria rats,the intestinal microbiota of healthy people was transplanted into the gastrointestinal tract of sterile rats in the healthy transplantation group,and the Chinese medicine group was administered by intragastric administration after fecal bacteria transplantation(Xingpi Jieyu Recipe,7.2g/kg/d),At the end of the 4th week,mitochondrial damage indicators(respiratory chain complex ? ? ? ? activity),mitochondrial biosynthesis pathway indicators(SIRT1,PGC-1? protein expression),mitochondrial energy indicators(ATP content,Na+-K+-ATPase activity,Ca2+-Mg2+-ATPase activity)to study the effect of depressive gut microbiota on the mitochondrial energy metabolism of rats,reveal the microscopic mechanism of depression microbes inducing depressive behavior,and clarify the effect mechanism of Xingpi Jieyu Recipe.Result:1.Mitochondrial damage index—complex ? ? ? ?Compared with blank control group and healthy transplantation group,? ? ? ?activity in hippocampus,skeletal muscle and small intestine tissue of depression transplantation group was decreased(P<0.01).Compared with depression transplantation group,hippocampus,skeletal muscle and small intestine tissue of Chinese medicine group Medium ? ? ? ? activity increased(P<0.01)2.Energy indicators—ATP,Na+-K+-ATPase,Ca2+-Mg2+-ATPaseCompared with the blank control group and healthy transplantation group,the ATP content of hippocampus,skeletal muscle and small intestine tissues decreased,Na+-K+-ATPase,Ca2+-Mg2+-ATPase activity decreased in depression transplantation group(P<0.01),compared with depression transplantation group In the traditional Chinese medicine group,the ATP content of hippocampus,skeletal muscle and small intestine increased,and Na+-K+-ATPase and Ca2+-Mg2+-ATPase activities increased(P<0.01)3.Mitochondrial biosynthetic pathway indicators—SIRT1,PGC-1?Compared with the blank control group and healthy transplantation group,the expression of SIRT1 and PGC-1? in hippocampus,skeletal muscle,and small intestine tissue of depression transplantation group were significantly decreased(P<0.01).Compared with depression transplantation group,SIRT1 in hippocampus,skeletal muscle,and small intestine tissue of traditional Chinese medicine group 2.The expression of PGC-1? increased(P<0.01)Conclusion:Depressive microbiota receptor rats have mitochondrial damage in hippocampus,skeletal muscle and small intestine,abnormal regulation of mitochondrial biosynthesis,and energy metabolism disorders,suggesting that the depressive microbiota can induce depression-like behavior in rats through mitochondrial damage.It has a protective effect on improving rat mitochondria and energy metabolism.Experimental study 3:Based on the cAMP-PKA-CREB-BDNF signaling pathway to study the mechanism of intestinal microbiota on rat depression-like behavior and the effect of Chinese medicine interventionObjective:To analyze the 5-HT-mediated cAMP-PKA-CREB-BDNF signaling pathway,reveal the microscopic mechanism of depression behavior induced by the depressive microbiome,and clarify the effect mechanism of Xingpi Jieyu RecipeMethods:8-week male sterile rats were randomly divided into blank control group,healthy transplantation group,depression transplantation group,and Chinese medicine group.The intestinal microbiota of patients with severe depression was transplanted to the depression transplantation group and the Chinese medicine group by fecal bacteria transplantation technology.In the gastrointestinal tract of bacteria rats,the intestinal microbiota of healthy people was transplanted into the gastrointestinal tract of aseptic rats in the healthy transplantation group.Study the cAMP-PKA-CREB-BDNF signaling pathway indicators(cAMP,PKA,CREB,BDNF)related to neuronal regeneration in the 4th weekend The influence of the pathway reveals the microscopic mechanism of depression-like behavior induced by the depressive microbiome,and clarifies the effect mechanism of Xingpi Jieyu RecipeResults:Compared with the blank control group and healthy transplantation group,the expression of cAMP,PKA,CREB,and BDNF in the hippocampus tissue of the depression transplantation group was significantly reduced(P<0.01).Compared with the depression transplantation group,the expression of cAMP,PKA,CREB,and BDNF in the hippocampus tissue of the traditional Chinese medicine group Increased(P<0.01)Conclusion:Depressive microbiota receptor rats have down-regulation of the hippocampal cAMP-PKA-CREB-BDNF signaling pathway,and cAMP-PKA-CREB-BDNF pathway-mediated abnormalities in emotion regulation,learning and memory,hippocampal neuronal regeneration,etc.are depressive microorganisms One of the biological essences of group-induced depression-like behavior in rats,XPJY recipe can up-regulate the hippocampal cAMP-PKA-CREB-BDNF signaling pathway,which has a protective effect against depression.