| Background:Pi housing Yi,which originated from Huang DI Nei Jing,is an important content of the theory of five spirit zang,has laid a solid theoretical foundation for the treatment of neurocognitive disorders in traditional Chinese medicine and has important theoretical significance and practical value.However,there is few experimental research reports on Pi housing Yi,and the scientific connotation and physiological mechanism of Pi housing Yi arc not systematically and thoroughly studied.What is the physiological mechanism of Pi housing Yi and how to make better use the traditional Chinese medicine theory of Pi housing Yi guides the treatment of cognitive disorders.It has become an important task for modern scientific research of traditional Chinese medicine theory.Objective:Collate the relevant literature,study the theoretical connotation of Pi housing Yi,and analyze the application of Pi housing Yi in the diagnosis and treatment of amnesia.Observe the influence of changes in intestinal flora on learning and memory ability and Pi and Wei function status based on the correlation between Pi and Wei and intestinal flora,and explore the modern scientific connotation and biological mechanism of Pi housing Yi from the perspective of learning and memory.Contents and methods:This research mainly involves two parts:literature research and experimental research.The first part is literature research.This part systematically elaborates the concept of the spleen from the perspective of anatomy and function,makes an in-depth summary of the mental activity process involved in the Yi housed in Pi,and explains the theoretical connotation of Pi housing Yi from the physiological basis and pathological characteristics;and discusses theoretically b ased on the academic views of the memory of the spleen hiding the mind,from the aspects of TCM’s understanding of amnesia,the theoretical basis and clinical application of Pi Wei to treat amnesia,and to provide an entry point and a foothold for the experimental research part.The second part is experimental research.This part explores the experimental conditions of establishing the animal mode of aMCI with phlegm dampness syndrome according to the effects of different fat to heat ratio and different exposure periods on the spatial learning and memory ability and TCM syndrome score of phlegm dampness syndrome in rats.Different doses of probiotic adminstration and Wendan Decoction intervention were taken after the successful establishment of aMCI with phlegm dampness syndrome,the relationships between the changes of intestinal flora,the functional state of Pi and Wei and the spatial learning and memory ability were studied by observing the changes of the score of phlegm dampness syndrome and the ability of learning and memory after probiotic administration,and the possible mechanism of action was studied according to the pathological changes of hippocampal tissues/neurons,the changes of synaptic plasticity and the diffcrences in the expression of neuromodulatory factors.The therapeutic effect of Wendan Decoction on aMCI with phlegm dampness syndrome was studied by observing the changing of the syndrome score,spatial learning and memory ability,pathological changes of hippocampal/neuron cells,synaptic plasticity and expression of neuromodulators after the intervention of Wendan Decoction,and whether Wendan Decoction play a role in preventing and controlling aMCI with phlegm dampness syndrome is analyzing by the consistency of the intestinal flora beteen Wendan Decoction group and the probiotic adminstration groupResults:1.Literature researchThe Pi of Pi housing Yi is a highly unified structure and function,which includes not only the spleen of the five organs,but also the functions of the viscera such as the Pi and Wei in the digestion of water and food,the regulation of Qi and the coordination of the viscera.The Yi of Pi housing Yi is a highly generalization of the psychological process like Soil such as memory,thinking,attention and will.Pi and Wei are the foundation of human being’s postnatal life,the source of Qi and Xue,and the hinge of Qi.thus,they can master and regulate mental activities such as memory and thinking.Amnesia is a kind of diseases characterized by memory loss and forgetfulness.Pi and Wei are responsible for the formation of memory,thus disorders of learnearning and memory are related to Pi and Wei.Amnesia is closely related to aging,and aging starts from the Pi and Wei,there is an inevitable causal relationship between the occurrence and development of Amnesia and the dysfunction of Pi and Wei.In addition,the imbalance of viscera and Qi Xue are also important factors leading to amnesia,which are closely related to Pi and Wei,Therefore,the treatment of forgetfulness should pay attention to Pi and Wei.The intestinal flora has complex biochemical characteristics,which is widely involved in various heart physiological activities of the host,including learning and memory activities.The intestinal flora is closely related to the Pi and Wei,which can reflect the functional state of the Pi and Wei to a certain extent,so we propose that regulating the intestinal flora is the key link of the therapeutic mechanism of regulating the Pi and Wei for amnesia.2.Experimental research(1)Establishment of aMCI rat model with phlegm dampness syndrome by inappropriate dietA.TCM syndrome score of phlegm dampness syndrome:compared with ain93 standard feed exposure,TCM syndrome score of phlegm dampness syndrome of 45%rats exposed to medium and high fat feed for 60 days increased(P<0.05);TCM syndrome score of phlegm dampness syndrome of 60%rats exposed to ultra-high fat feed for 30 days and 60 days increased significantly(P<0.01).B.Sp atial learning and memory ability:compared with AIN93 standard diet exposure,60%ultra-high fat diet exposure for 60 days significantly reduced the swimming time in the target quadrant(P<0.05).(2)The effect and mechanism of probiotic management/Wcndan Decoction on aMCl rats with phlegm dampness syndromeTCM syndrome score of phlegm dampness syndrome:Compared with the standard control group,the TCM syndrome score of phlegm dampness syndrome in the high-fat control group was higher(P<0.01);compared with the high-fat control group,the TCM syndrome score of phlegm dampness syndrome in the low-dose(probiotic adminstration)group and the middle dose group had no significant difference(P>0.05),the TCM syndrome score of phlegm dampness syndrome in the high-dose group was lower(P<0.05),and the TCM syndrome score of phlegm dampness syndrome in the Wendan Decoction group was lower(P<0.05)TCM syndrome score decreased significantly(P<0.01).B.Spatial learning and memory ability:Compared with the standard control group,the swimming time in the target zone of the high-fat control rats was reduced(p<0.05);compared with the high-fat control group,the swimming time in the target zone of the low-dose and middle-dose groups had no significant difference(p>0.05),high-dose group was increased(p<0.05),and Wendan Decoction group was increased significantly(p<0.01).C.Pathological observationa.He staining:the number of neurons in CAl area and DG area of hippocampus in each group was abundant,the morphology was basically normal,the arrangement was regular,the boundary between nucleus and cytoplasm was clear,he staining showed no obvious abnormality.b.Toluidine blue staining:The number of Nissl bodies in the hippocampus tissue of the standard control group is rich,deeply stained,and distributed in plaques.In the high-fat control group,the number of Nissl bodies in the hippocampus was relatively small,and the positions were relatively scattered,and the staining became lighter.The number of Nissl bodies in the hippocampus tissues of the high-dose group and the Wendan decoction group was rich,and the staining degree of the rats in the higher-fat control group was deepenedc.Ultrastructure of neurons in hippocampus:The neurons in the hippocampus of the standard control group were basically normal in shape and structurally intact,with abundant organelles in the neurons and no obvious abnormalities in the cytoplasmic matrix.In the high-fat control group,the neuron cells in the hippocampus showed severe edema,the cytoplasmic matrix was reduced,the number of organelles was significantly reduced,and most of them were necrotic and disintegrated.In the high-dose group,the neurons in the hippocampus of the rats showed moderate edema,the intracellular organelles were abundant,but they all had different degrees of swelling.The neuron cells in the hippocampus tissue of the Wendantang group showed moderate edema,the cell membrane structure remained,and were swollen to varying degrees.d.Hippocampal tissue synaptic ultrastructure:the standard control group of rats has a complete synaptic structure,thicker presynaptic membrane,thicker postsynaptic membrane,narrow synaptic space,and synaptic vesicles Abundant;the high-fat control group had severe edema of the synapse structure,the dense area of the presynaptic membrane was thin,the structure was unclear,the synaptic gap widened,and there were fewer synaptic vesicles;the high-dose group had moderate synapse Edema,presynaptic membrane protein aggregation,dense areas are thicker,synaptic gaps are slightly wider,and synaptic vesicles are abundant Rats in the Wendan Decoction group had moderate edema of the synapse structure,sparse presynaptic membrane protein,thin dense area,relatively dense area of the post-synaptic membrane,slightly widened synaptic gap,and abundant synaptic vesicles.D.Long-term potentiating effect of hippocampal CA3-CA1:Compared with the standard control group,the fEPSP slope of the high-fat control group rats was reduced after HFS induction(p<0.05);compared with the high-fat control group,the high-dosc group probiotics after HFS induction,the slope of fEPSP increased sign ificantly(p<0.01),and the fEPSP slope of rats in Wendan Decoction group increased after HFS induction(p<0.05)E.Expression of ncurorcgulatory factors:Compared with the standard control group,the expression levels of BDNF,CREB and SYP in hippocampus tissues of the high-fat control group were reduced(p<0.01 or p<0.05);The expression level increased(p<0.05),and there was no significant change in SYP(p>0.05);the expression levels of BDNF(p<0.01),CREB and SYP(p<0.05)in hippocampus tissue of rats in Wendan Decoction group increasedF.Change of intestinal flora:Alpha diversity analysis showed that compared with the standard control group,the Chaol index and Observed species index of the high-fat control group decreased significantly(p<0.01);compared with the high-fat control group,the Chaol index and Observed species index of the high-dose group increased significantly,Chaol index and Observed species index of Wendan Decoction group increased(p<0.05 or p<0.01).Species relative abundance analysis showed that compared with the standard control group,the relative abundance of Bacteroides in the high-fat control group decreased,while the relative abundance of Blautia and Clostridium XlVb and Paraprevotella increased;The relative abundance of Bacteroides in the high-dose group and Wendan Decoction group increased,while the relative abundance of Blautia,Clostridium XlVb and Collinsella decreased,and the trends were similar.OTU analysis showed that the standard control group and the high-fat control group had significant differences in the intestinal flora species composition;the high-dose group and the Wendan Decoction group had similar intestinal flora species composition to the standard control group.Conclusion:1.Literature researchThe meaning of Pi housing Yi refers to the hosting and regulating effect of Pi and Wei on psychological processes such as memory and thinking in mental activities.Pi and Wei are the foundation of human being’s postnatal life,the source of Qi and Xue,and the hinge of Qi.thus,they can master and regulate mental activities such as memory and thinking.Pi housing Yi is the theoretical basis of traditional Chinese medicine treating psychosis from Pi and Wei.2.Experimental research(1)60%ultra-high fat diet exposure for 60 days can successfully establish the rats model of aMCI with phlegm dampness syndrome.(2)High-dose probiotic adminsrtration can regulate intestinal flora,significantly improve the function of Pi and Wei the phlegm-dampness aMCI model rats,regulate the expression of BDNF and CREB,proomote the repair and growth of neurons,improve the long-term synaptic plasticity,and thus improve the spatial learning and memory ability of rats.Intestinal flora is closely related to the Pi and Wei,and the intestinal flora can reflect the function of the Pi and Wei to a certain extent,which is one of the biological bases of the Pi housing Yi.(3)Wendan Decoction can reduce the severity of phlegm dampness syndrome in aMCI rats induced by high fat diet,regulate the expression of BDNF,CREB and SYP,promote the repair and growth of hippocampal neurons,increase the long-term synaptic plasticity,and improve the ability of spatial learning and memory After the intervention of Wendan Decoction,the change trend of intestinal flora was similar to probiotic adminstration.Wendan Decoction could regulate the intestinal microecology of rats with high fat diet.After intervention of Wendan Decoction,the species composition of intestinal flora and the trend of species diversity was similar to that after high-dose probiotic administration.Regulation of intestinal flora might be one of the key links of the mechanism of Wendan Decoction in the prevention and treatment of phlegm dampness middle resistance type aMCI induced by high-fat diet. |
PDF Full Text Request