Study On The Law And Mechanism Of Tibetan Medicine's Prevention And Treatment Of Plateau Disease Based On Knowledge Discovery

Plateau disease also known as mountain sickness.The air is thin,atmospheric pressure and oxygen partial pressure is low in the mountains and highland areas(above 3,000 meters above sea level),the body of this hypoxic environment adaptability or disorders caused by syndrome.In our country,more than 3,000 meters above sea level in the region accounted for about 1/6 of the total land area,the high altitude sickness threatened the aborigines in these areas and other people into these areas,and then the country's political,economic,military and other aspects Serious impact.Therefore,how to prevent and cure highland disease has become China's plateau life science needs to focus on solving the key issues.The Tibetan people who have lived in the Tibetan Plateau have created a splendid culture in the history of thousands of years.Among them,the Tibetan medicine culture of self-contained system is a wonderful work in the blooming of our national medicine garden.It can be said that there are few people in the world who are familiar with the plateau,love the plateau,and adapt to the plateau.They are "cultivating the Tibetan medicine culture according to local conditions" and "born" to the rich resources of the plateau disease.A very valuable asset.However,slightly regret that,although the Tibetan medicine in the prevention and control of high altitude disease has a unique advantage,but its drug characteristics and compatibility principles are still lack of systematic order,mining,Tibetan medicine plateau disease mechanism is not clear enough,specific;Over the years to record the Tibetan physician's clinical experience,experience books and books continue to produce,but the pulse of the development of disciplines only through the traditional manual search method can not accurately capture.It is an important task to extract useful knowledge of high altitude disease from the vast literature information.Bibliometrics,knowledge visualization,data mining and other methods is an effective means to solve these problems.This study focused on high altitude disease,with effective knowledge discovery as the goal,combined with the use of bibliometrics knowledge map,data mining technology,network pharmacology method,for the high disease disease construction of multidimensional literature research model;through the analysis of domestic and foreign high disease research The status quo,found its hot spots and trends,to explore the Tibetan medicine treatment of plateau disease medication law,reveal the role of Tibetan medicine plateau disease mechanism,highlighting the advantages of Tibetan medicine prevention and control of plateau disease.Objective:(1)Through the domestic and foreign research on the development of plateau disease bibliometrics and knowledge map visual analysis,finishing the development of highland disease research in the field of the main clues to show its representative units and academic leaders,analysis of knowledge domain structure,found that the field of research,Forecast the development trend,grasp the current situation of highland disease research at home and abroad,for scientific research workers to provide data reference,research direction.(2)Through the systematic analysis of Tibetan medicine plateau disease side,the representative medicine,drug mode and core combination of Tibetan medicine treatment of plateau medicine were found,and the medicine rule and compatibility mechanism of Tibetan medicine prevention and control of plateau disease were found.Screening for reference.(3)To study the key targets and significant pathways of the role of Sangjiang Decoction in the treatment of plateau polycythemia by using the method of data mining.The knowledge found to provide new ideas.Methods:(1)Based on SCI and CNKI database,the literatures of plateau disease published at home and abroad were analyzed by means of word frequency analysis and cooccurrence analysis.The literatures were analyzed from the aspects of age,author and source institution.Research group,the leading person;using information visualization software Cite Space3.8R1 to draw the knowledge map of highland disease research at home and abroad,through the literature co-cited cluster analysis,keyword coclustering analysis,identify the field of high school disease research hotspots and Research frontier,development trend.(2)To "plateau disease","plateau polycythemia","mountain","plateau discomfort","chronic high disease","plateau blood pressure","blood","blood Peking" and other related terms as keywords,search for "Tibetan prescription dictionary","national medicine into prescription","basic Tibetan medicine" and Sichuan Tibetan medicine into the preparation of the database to meet the inclusion criteria of altitude sickness agents,and reference "Tibetan medicine" "Chinese Pharmacopoeia" "Chinese herbal medicine" "Tibetan medicine" "crystal beads Materia Medica" "Chinese herbal medicine Daquan" "Chinese national medicine dictionary" and other standards,the establishment of Tibetan medicine prevention and control of high altitude diseasedatabase,Auxiliary platform,the use of association rules,entropy clustering and other data mining methods for frequency statistics,prescription rules,the new party combination analysis,to explore the Tibetan medicine prevention and treatment of plateau disease drug use characteristics.(3)Through the TCMSP database,the chemical constituents of the phytoplankton were selected by PharmMapper,and the potential targets were introduced into the MAS 3.0 database for the target annotation and analysis.Combined with the KEGG database The results showed that the mechanism of the treatment of copycatemphonphyllanthus embolus was the most important factor in the treatment of secondary polycythemia by using Cytoscape software,and the mechanism of "componenttarget" and "target-pathway".And provide a methodological reference for the study of the mechanism of action of Sanjiang Decoction.(4)Based on the study of the mechanism of the combination of myrobaly and Phyllanthus emblica,the pharmacological effects of the three fruit soup and the oral administration of the TCMSP database and the pharmacological analysis were used to screen the effective effects of Decoction of Three Fruits.The HOMC pathogenesis was used to predict the target by ChemMapper server.Using the relevant database,the predicted target is annotated and analyzed.The cytological experiments were performed by CKK8 and enzyme-linked immunosorbent assay(ELISA)for significant pathway(VEGF pathway).Results:Based on the analysis of bibliometric knowledge:(1)The analysis of international highland disease research literature: 2011-January 2017,the United States,Britain,China,Switzerland is the main country of high disease research,high altitude disease research involving a total of 59 studies Direction,content to the respiratory system,cardiovascular system,physiology and so on,the fund funded the share of more papers,and the main public funds.Research hot spots: "high altitude","hypoxia","pulmonary hypertension","gene expression" and so on.(2)Domestic plateau disease research literature analysis: 2006-2016,the domestic plateau disease research mainly involves 31 research directions,including endocrine,military medicine,cardiovascular and other disciplines.The first two were the author of the 18 th Hospital of the People's Liberation Army Institute of Alpine Disease Cui Jianhua,Qinghai University Affiliated Hospital Cui Sen,the highest is the third largest military medical high Yu Qi,they have high academic research in the field of high disease.Fund funded by the proportion of more than 50% of the literature,mainly to the national and provincial funds.The research hotspots are: "Plateau polycythemia","high altitude","acute altitude sickness","chronic high disease","apoptosis","high altitude hypoxia","pulmonary hypertension" and so on.(2)Through the data mining research,a total of 531 Tibetan medicine prevention and control of disease prevention and treatment of disease,the common symptoms of treatment are insomnia,swelling,tinnitus,headache,etc.;Fang total involving 539 herbs,the total drug frequency of 6138 times,With the frequency of ? 50 with arousal,nutmeg,woody,safflower and other 33 flavor,which the highest use of myrobalan,Phyllanthus emblica,Maobian use frequency is also more than 100 times,the use of frequency ranking;Prescription traditional Chinese medicine flavor to the main drug,accounting for 43.834%;for high altitude disease commonly used drug combination14,"woody-myrobalan" use the highest frequency to cluster algorithm analysis,commonly used combination: clove-,Saxifraga-down incense,possession of Lithospermum-Ganqing Qinglan,duckbill flowers-incense,incense-horse money and so on.Based on the complex system of entropy clustering of the core combination of 13,including: garlic-fennel-ferulic,alkali flower-cold water stone-borax,wood-incense-clove-nutmeg,wood-sweet date-incense-nutmeg Wait.Candidate new party:(1)garlic,possession of fennel,ferulic,woody,jujube,incense,nutmeg.(2)papaya,rice,acid rattan fruit,millet spicy,big care leaves cloud real.(3)rhubarb,alkali flowers,cold water stone,borax.(4)Piper Long,pomegranate,cinnamon,white cardamom.(5)hand ginseng,yellow fine,aspartic,Himalayan Mirabilis,Tribulus terrestris.(3)Twenty-four chemical constituents were identified by the combination of "Huizhi-Yu Ganzi",which was related to 261 targets,and 117 targets and 59 channels were associated with secondary erythrocytosis.MAPK1(Mitogen-activated protein kinase 1),AR(androgen receptor),ADH1C(alcohol dehydrogenase 1C),ADH5(tertiary alcohol dehydrogenase),MET(hepatocyte growth factor receptor),EGFR Growth factor receptor)as a key target to retinol metabolism pathway(Retinol metabolism)as the representative of the cell proliferation pathway,metabolic pathway has an advantage.(4)A total of 193 and 70 signaling pathogens were found in Decoction of Three Fruits,and 24 targets and 25 channels were associated with HAPC,and the three pharmacological methods were combined with the network pharmacological method.MAPK12(mitogen-activated protein kinase 12),RAC1(RAS-associated botulinum toxin substrate 1),MAPK12(mitogen-activated protein kinase 12),AKT1(RACalpha serine / threonine-protein kinase)May be the key target,VEGF signaling pathway(VEGF signaling pathway),Fc epsilon RI signaling pathway(Fc?RI signaling pathway),Toll-like receptor signaling pathway(Toll-like receptor signaling pathway)and other channels.The concentration of VEGF in the supernatant of the blank group was the highest,and the concentration of VEGF in the blank group was higher than that in the blank group(P <0.05),and the concentration of VEGF in the blank group was higher than that in the blank(P <0.05).There was significant difference between the two groups(P <0.05).After 48 h,the expression of VEGF Mrna in the rats with high red blood cells(simulated K562 cells)was significantly higher than that in the control group(P <0.05)(P <0.05),and the difference was significant(P <0.05).Conclusions:Europe and the United States in the field of high disease disease research in the field,domestic and foreign high disease research investment is on the rise;Tibetan medicine advantage is not highlighted;high altitude disease research direction is uneven;domestic and foreign high disease research hot spots are slightly different Concerned about pathogen disease research,the international community is also concerned about the genetic aspects of high altitude disease research,the domestic plateau polycythemia,chronic high altitude disease as a research focus.China should take the European and American countries as the benchmark,continue to increase investment in scientific research and personnel training,strengthen institutional cooperation and international cooperation,exchange and explore the conditions of highland disease research principles and policies,give full play to the advantages of Tibetan medicine,Erythrocytosis as the representative of the study of hot research,effective knowledge found to enhance the relevant research field of international status.(2)Tibetan medicine treatment of plateau disease medication law: mainly to myrobalan as the representative of Decoction of Three Fruits scattered as the basic source,according to the different pathogenesis often compatibility nourishing the nerves,temperature in the gas,Spleen and Stomach,Blood stasis and other highfrequency combination of drugs.Heat and cooling blood,digestion and stomach,Help Produce Saliva And Slake Thirst,Detoxification,convergence of blood as the main drugtendencies.(3)Myrobalan – Phyllanthus emblica combined with MAPK1,AR,ADH1 C,ADH5,MET,EGF and other key targets,affecting cell reproduction,endocrine metabolism,inflammatory response and other processes,synergistic effect of secondary polycythemia.This study can provide a methodological reference for the study of HAPC mechanism.(4)The results showed that the main active ingredients such as polyphenols,flavonoids and terpenoids in Decoction of Three Fruits could enhance the immune function and hypoxia stress by participating in cell proliferation,oxidative reaction,endocrine metabolism and inflammatory reaction,And thus multi-target,multichannel synergies to play the role of anti-HAPC,in order to demonstrate the results of pre-research,but also for the Tibetan medicine prevention and treatment of plateau disease mechanism to provide a new idea.Innovations:(1)Research ideas novel – the first use of high altitude disease research of the overall view of multidimensional literatureFor the first time,the bibliometrics knowledge map,data mining technology and network pharmacology method are effectively integrated for the research trend of plateau disease,and the knowledge discovery of Tibetan medicine prevention and treatment of plateau disease and the mechanism of knowledge discovery,and strive to ensure the scientific results of research results Objectivity,can provide a methodological reference for the standardization of standardized disease and standardized research.(2)Study on the mechanism of network pharmacology for the first time to introduce Tibetan medicine into Decoction of Three FruitsIn this study,we follow the international frontier and choose the network pharmacology method with high maturity as the research technique to analyze the compound-target-disease network,and study the complex relationship between multiple targets and multiple diseases,This paper mainly explores the regulation mechanism of Tibetan medicine compound intervention in molecular signaling pathway of plateau disease.For the first time,this new technique has been introduced into the research of Tibetan medicine prescription Decoction of Three Fruits and its representative drug combination.The technical means are advanced,which is beneficial to knowledge discovery and strong innovation.(3)Drug of mechanism example is typical and representativeIn this study,under the guidance of Tibetan medicine theory,through the data mining found that Tibetan medicine treatment of plateau disease medication rules,summed up the selection of the basic combination of plateau disease – Decoction of Three Fruits scattered.The party is not only the “four medical code” classic side,the use of a long history,but also Tibetan medicine bleeding therapy before the use of the choice of Decoction of Three Fruits as a Tibetan medicine prevention and treatment of plateau disease mechanism of drug research model,has a certain typical and representative.