| Objective:This study focused on the treatment of vascular dementia(VD)with treating phlegm and blood stasis simultaneously from four aspects:theoretical study,knowledge map,clinical trial and animal experiment.The theoretical part is based on the viewpoint of "intermingled phlegm and blood stasis" in TCM,excavates its theoretical connotation,analyzes the understanding of "phlegm","blood stasis" and "knot" in TCM,and the rationality of treating VD with simultaneously treat phlegm and blood stasis.In the part of knowledge mapping,literature metrology and Cite Space were used to analyze and summarize the current research status of intermingled phlegm and blood stasis,explore the research hotspot in this field,and predict its future development trend.Part of the clinical trial was based on the theory of "intermingled phlegm and blood stasis" to observe the clinical efficacy of the treatment of VD patients with simultaneously treat phlegm and blood stasis.In the animal experiment,improved bilateral common carotid artery ligation method was used to establish VD rat model,and the intervention effect and possible mechanism with treating phlegm and blood stasis simultaneously on VD rats were analyzed by behavioral and pathological methods.Method:1.Theoretical discussion By searching relevant literature,sorting out relevant ancient books,and systematically summarizing various methods,from the viewpoint of "intermingled phlegm and blood stasis",excavate its theoretical connotation,and analyze the understanding of "phlegm","blood stasis" and "stagnation" in TCM,analysis of its concept,development and evolution,physiological functions etc.in-depth,to explore the understanding of traditional Chinese and Western medicine on the relationship between intermingled phlegm and blood stasis and inflammatory response,to analyze the rationality and scientificity of treating phlegm and blood stasis simultaneously in the treatment of VD,and lay the foundation for us to establish the method and prescription of treating phlegm and blood stasis simultaneously.2.Knowledge Graph Used Cite Space software to analyze the authors,institutions,keywords and other information contained in the journal literature related to the research in the field of intermingled phlegm and blood stasis,obtained a visual knowledge graph,and descriptive information such as fund funding and journal sources.The author's cooperation and institutional cooperation of the research on intermingled phlegm and blood stasis syndrome were sorted out,and its different research topics were summarized.3.The clinical study Collected VD patients who were admitted to the Department of Encephalopathy,Hubei Provincial Hospital of TCM,the National Medical Hall of Hubei University of TCM,and the Department of Neurology of Wuhan First Hospital from September 2020 to September 2021.Sixty-four patients who conform to the diagnostic criteria and inclusion criteria were randomly divided into two groups.The control group was given oral administration of Donepezil Hydrochloride Tablets(Aricept),and the experimental group was given oral administration of Tanyu Tongzhi Granules.The treatment period was 12 weeks,and all the enrolled patients were collected before the intervention and within 12 weeks(± 3 days)of the intervention,including TCM syndrome scores,cognitive function and daily living ability,to evaluate the clinical efficacy of treatment in VD with treating phlegm and blood stasis simultaneously.4.Experimental research(1)SPF male SD male rats,weighing 250±10g,were adaptively reared for 1week and then started the experiment.They were randomly divided into 4groups,namely the sham operation group,the model group,the treating phlegm and blood stasis simultaneously group,and the donepezil group,with10 rats in each group.The VD rat model was established by the modified bilateral common carotid artery ligation method,and each group of rats were given corresponding intervention measures.(2)The Morris water maze test was used to detect the changes of learning and memory ability of VD model rats.The changes of hippocampus morphology of rats were observed by HE staining and ultra-electron microscope.To explore the changes of learning and memory ability of VD model rats and the intervention effect on pathological injury of hippocampus by treating phlegm and blood stasis simultaneously.(3)Real-Time PCR was used to detect the transcription level of TLR4/My D8/NF-?B pathway m RNA in the hippocampus of VD rats;Western blotting method was used to detect the expression of related proteins TLR4,My D88 and NF-?B p65 in the hippocampus of VD model rats;ELISA method was used to detect the levels of TNF-?,IL-1? and IL-6 in the hippocampus of VD model rats,and to explore the effect of treating phlegm and blood stasis simultaneously on the inflammatory response of VD model rats.Result:Theoretical discussion: TCM has a very rich theoretical origin about "intermingled phlegm and blood stasis".The understanding of "phlegm","blood stasis" and "stagnation" is relatively comprehensive.It was closely related to the inflammatory response of modern medicine.Treating phlegm and blood stasis simultaneously is an important method for our treatment of VD.Based on this treatment method,the research group established the traditional Chinese medicine formula and carried out relevant clinical and experimental studies to clarify the clinical effect of the treatment on VD patients and the mechanism of action on VD rats,to provide new ideas and methods for guiding clinical practice.Knowledge map: The vast majority of research in the field of intermingled phlegm and blood stasis syndrome was carried out on the basis of diseases.Judging from the co-occurrence results of authors,5 stable representative cooperative teams have been formed.Judging from the co-occurrence and clustering results of keywords in the journal literature,there are relatively many scholars and teams focusing on the research of intermingled phlegm and blood stasis syndrome of related diseases,or the research on the diagnostic criteria;Judging from the co-occurrence results of institutions,the cooperation between institutions is relatively close,and there are many cross-regional cooperation.Clinical trial: Both the experimental group and the control group can reduce the TCM syndrome scores of VD patients,and significantly improve the related TCM syndromes,the clinical efficacy of the experimental group is better than that of the control group.Both the experimental group and the control group can effectively improve the MMSE score of VD patients,the clinical efficacy of the experimental group is better than that of the control group,and the cognitive function of the patients is significantly improved.Both the experimental group and the control group can effectively reduce the ADL score of VD patients,and clinical efficacy were similar in improving the daily living ability of VD patients.Animal experiment: Experiment 1: Compared with the model group,the total swimming distance and the escape latency of the VD rats in each administration group were shortened,the times of crossing the platform were increased,and the residence time in the target quadrant was prolonged.Experiment 2: HE staining results: Compared with the model group,the cell structure of the hippocampus CA1 region of the rats in the treating phlegm and blood stasis simultaneously group was relatively complete,the cell morphology was more regular,the number of normal cells was more,the arrangement was neater,and the nuclear membrane and nucleolus were clearer.It can be seen that some nucleoli are pyknotic and hyperchromatic,and the cytoplasm was more abundant,which is better than the model group.Ultra-electron microscopy results: Compared with the model group,the neuron structure of the treating phlegm and blood stasis simultaneously group was more complete,the degree of cell membrane dissolution was lighter,the partial ridges of mitochondria were intact,and the cavitation and expansion were significantly lighter than those in the model group.It was suggested that that the treating phlegm and blood stasis simultaneously could improve damage to the cellular structure of the hippocampus in VD rats.Experiment 3:Real-Time PCR results: Compared with the sham operation group,the expression of TLR4 m RNA,My D88 m RNA and NF-?B p65 m RNA in the model group were increased.Compared with the model group,the expressions of TLR4 m RNA,My D88 m RNA and NF-?Bp65 m RNA in each administration group were decreased.The expression of TLR4 m RNA and NF-?B p65 m RNA in the treating phlegm and blood stasis simultaneously group were lower than those in the donepezil group,and the expression of My D88 m RNA was not significantly different from that in the donepezil group.Western blot detection results: Compared with the sham operated group,the relative expressions of TLR4,My D88,and NF-?B p65 proteins in the hippocampus of the model group were increased.Compared with the model group,the relative expressions of TLR4,My D88 and NF-?B p65 proteins in each administration group were decreased.Compared with donepezil group,the expression of TLR4 and NF-?B p65 protein in treating phlegm and blood stasis simultaneously group decreased more significantly,and the relative expression of My D88 protein was not significantly different.ELISA test results: Compared with the sham operation group,the contents of TNF-?,IL-1? and IL-6 in the hippocampus of the rats in the model group were increased.Compared with the model group,the contents of TNF-?,IL-1? and IL-6 in the hippocampus of the rats in each administration group decreased.The levels of TNF-?,IL-1? and IL-6 decreased in the donepezil group and the treating phlegm and blood stasis simultaneously group were similar,and the difference was not statistically significant.Conclusion :(1)Intermingled phlegm and blood stasis is the key to the pathogenesis of the occurrence and development of VD,and is closely related to the inflammatory response.The treating phlegm and blood stasis simultaneously is an important treatment method for VD,which can treat VD by inhibiting the inflammatory response.(2)At present,the research on intermingled phlegm and blood stasis has formed multiple research teams and different research themes,and the number of relevant research literature publications has increased year by year.Clinical efficacy research,TCM syndrome distribution research and correlation research with biological indicators,etc.,the diseases involved include coronary heart disease,hypertension,hyperlipidemia,diabetes,vertigo,mammary gland hyperplasia,dementia,rheumatoid arthritis,acne,etc..The cooperation between research institutions is relatively close.(3)The treatment of treating phlegm and blood stasis simultaneously can effectively reduce the TCM syndrome scores of VD patients,improve the cognitive function of VD patients,and improve their daily living ability.There were no serious adverse reactions in the two groups of patients during the whole study process,and it had good safety.(4)There are pathological changes in the hippocampus in the VD model rats,and their learning and memory abilities are significantly reduced,indicating that the establishment of the VD rat model is successful.(5)The treatment of treating phlegm and blood stasis simultaneously can effectively improve the learning and memory ability and the pathological damage of hippocampus in VD model rats.(6)The treatment of treating phlegm and blood stasis simultaneously can inhibit the TLR4/My D88/NF-?B signaling pathway in the hippocampus,reduce the expression of TLR4,My D88,NF-?B.Reduce the levels of TNF-?,IL-1? and IL-6 in the hippocampus of VD rats,and alleviate the inflammatory response in VD rats. |
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