Research On The Inheritance And Mechanism Of The Treatment Of Type 2 Diabetes With Clearing Away Heat And Nourishing Qi

Type 2 diabetes mellitus(T2DM)is an endocrine and metabolic disease based on the pathophysiology of insulin resistance and insufficient insulin secretion.Various acute and chronic complications caused by diabetes seriously affect the physical and mental health and quality of life of patients.Chinese medicine has unique advantages in preventing and treating diabetes and its complications,The key discipline of endocrinology in Dongzhimen Hospital of Beijing University of traditional Chinese medicine attaches great importance to clearing away heat and benefiting qi in the treatment of diabetes,and has achieved good clinical effect.In this paper,the combination of data mining,network pharmacology and animal experiments is used to explore the regularity of the heat-clearing and qi-relieving method and the mechanism of action of related drugs,providing clinical application and scientific research for the treatment of type 2 diabetes Data support and scientific basis.purpose1.Through data mining method,the academic thought and inheritance characteristics of Professor Lu Renhe and his academic successor Professor Zhao Jinxi's experience in the treatment of type 2 diabetes are combed,and the clinical medication law guided by the method of clearing away heat and benefiting Qi of diabetes is revealed.2.Based on the analysis of network pharmacology,the target and mechanism of Coptis chinensis and Panax ginseng in the treatment of type 2 diabetes mellitus were explored,which provided ideas for further experimental research.3.Based on the doctrine of inflammation of type 2 diabetes and the doctrine of intestinal flora,through animal experiments,the anti-inflammatory mechanism of Coptis chinensis and ginseng "drug pairs" in the treatment of type 2 diabetes was clarified.method1.Quantitative research methods such as descriptive statistics,association rules,system clustering,naive Bayes and support vector machines are used to summarize the academic thoughts and experience inheritance characteristics of Lu Renhe and Zhao Jinxi in treating diabetes.2.Through the network pharmacology analysis method,the chemical components of Coptis chinensis and ginseng were screened using the TCMSP platform,and the drug active components and T2DM related targets were screened using STITCH,DrugBank,TTD,GAD and DisGeNET databases.Cytoscape software is used to construct the network,and the biological function and pathway enrichment analysis of the target is performed through the David database.3.Db/db mice were randomly divided into model group,metformin group,Coptis chinensis and ginseng group,and db/m mice were used as blank control group.Through Western blotting and other techniques,the blood glucose,body weight,LPS,inflammatory factors,NF-?B p65,p-NF-?B p65,TLR4 and other indicators were detected.At the same time,16srDNA sequencing technology was used to analyze the intestinal flora of mice.Finally,from the perspective of regulating the intestinal flora,the mechanism of anti-inflammatory and improvement of insulin resistance of Coptis chinensis and ginseng medicine are clarified.result1.?A total of 692 effective cases were included in this study,including 323 cases by Lu Renhe and 369 cases by Zhao Jinxi.There are 354 males and 338 females.In the medical records included,the most common syndromes are internal heat syndrome,yin deficiency syndrome,Qi deficiency syndrome and blood stasis syndrome.The top 10 are dry mouth,fatigue,poor sleep,suffering,numbness,dry stool,dizziness,blurred vision,irritability.Dry mouth and fatigue are the most frequent symptoms of diabetes,reflecting the pathogenesis characteristics of "heat hurts Qi Yin" of diabetes.Among the diabetic patients,the most common syndrome of depression is characterized by bitter mouth(1.657),irritability(1.599),tinnitus(1.185),fever(1.061),dry moss(0.972),fullness of chest and flank(0.761)and turbid foam(0.735).Smo analysis showed that the weight of sublingual collateral stasis was higher in the syndrome of heat accumulation,sighing was higher in the syndrome of qi deficiency,forgetful and purple dark tongue quality was higher in the syndrome of damp heat,stomachache,ecchymosis on the tongue and halitosis were higher in the syndrome of Yu heat,which may provide some ideas for the syndrome differentiation and treatment of related symptoms.Professor Lu Renhe and Professor Zhao Jinxi all used more Chinese medicine with cold nature,followed by warm nature.?According to the association rules and cluster analysis,we found the common drug pairs of Citri Fructus and Citri Sarcodactylis Fructus,Linderae Radix and Cyperi Rhizoma,Persicae Semen and Carthami Flos,Radix Puerariae and Radix Salviae.In the analysis of association rules,it was found that the only heat-removing medicine and Qi-invigorating medicine with association relationship were Coptidis Rhizoma and ginseng(confidence 0.912).?Through simple Bayesian analysis,we found that Pinellia ternate(0.775),Coptis chinensis(0.704),Pueraria(0.769),Poria Cocos(0.577),Anemarrhena(0.352),Trichosanthes(0.31)were more frequently used in phlegm heat syndrome,and raw Rehmannia(0.462),Figwort(0.385),Glehnia Littoralis(0.359),smallpox(0.179),cooked rhubarb(0.179),Angelica(0.179),Peony bark(0.128)were more frequently used in heat accumulated syndrome Among them,Scutellaria(0.877),Radix paeoniae Alba(0.79),Radix Paeoniae Rubra(0.525),bupleurum(0.796),tangerine peel(0.673)were mostly used in syndrome of stagnated heat of liver channel;Atractylodes macrocephala(0.447),rhizoma atractylodis(0.319),Phellodendron amurense(0.213),Radix Cyathulae(0.128),Achyranthes bidentata(0.149)were mostly used in damp heat syndrome.?Through Bayesian and SMO analysis,we further found the internal relationship among syndrome and traditional Chinese medicine.For example,in Lu Renhe's case:Yin deficiency-dysphoria in chestpalms-soles(2.149)-Gardenia(0.571),yin deficiency-night sweat(1.77)-Peony bark(0.688),syndrome of stagnated heat of liver channel-dysphoria with smothery sensation(1.061)Peony bark(0.667).In Professor Zhao Jinxi's medical case:syndrome of stagnated heat of liver channel-bitter taste(1.657)-Scutellaria(0.887),syndrome of stagnated heat of liver channel-tinnitus(1.185)-Scutellaria(0.886),yin deficiency-night sweat(1.77)-raw Rehmannia(0.522),yin deficiency-dysphoria in chestpalms-soles(2.149)-wolfberry bark(0.846).2.Through network pharmacology analysis,the active ingredients and targets of Coptis chinensis and Ginseng were screened,and 144 targets of ginseng,246 targets of Coptis chinensis,and 350 targets of type 2 diabetes were obtained.Matching obtained 42 potential targets of TCM pharmacological treatment of Coptis chinensis and ginseng.Among the main active ingredients of Coptis chinensis and ginseng "drug pairs",quercetin,berberine,kaempferol,arachidonic acid,ferulic acid,stigmasterol,etc.,have many predicted targets.These compounds may be Ginseng "drug pair" is an important compound that produces pharmacological effects.The core targets of Huanglian and ginseng drugs for the treatment of type 2 diabetes are related to drug metabolism,insulin resistance,and inflammatory response,and are involved in the AMPK signaling pathway,NF-?B signaling pathway,TNF signaling pathway,and glucagon signaling pathway.Targets TNF and IL1B are the common targets of NF-?B signaling pathway and TNF signaling pathway.We speculate that Coptis chinensis and ginseng drugs have an anti-inflammatory effect by regulating the intestinal flora and correcting the activation of LPS/NF-?B/inflammatory pathways caused by disturbance of intestinal flora.3.? Observation of the general condition of the mice revealed that the db/m mice had a bright coat,agile movements,slender body,and agile activities,and responded greatly to external stimuli.However,the db/db mice are obese,slow in movement,less active.increased ingestion and drinking,and are obviously slow to respond to external stimuli.In the later period of intragastric administration,the model group again showed vertical hair and low body temperature,and individual mice of the model group experienced a sudden weight loss in the last week.The weight of mice in other groups increased basically steadily.?After 8 weeks of intragastric administration of Coptis chinensis and ginseng,the blood glucose of the mice decreased significantly.Coptis chinensis and ginseng medicine can significantly reduce the expression of IL1? in the pancreas of type 2 diabetic mice and inhibit the expression of p-NF-?B p65/NF-?B p65 in the liver of diabetic mice.? In this study,it was found that the total number of OTUs in the gut microbes of the blank control group and the model group was 543,accounting for 71%of the total of the two groups.The big difference is that the intestinal microbial abundance and diversity of non-diabetic mice are significantly smaller than those of diabetic mice,which is inconsistent with some previous experimental results,and the intervention of traditional Chinese medicine also significantly reduced the intestinal microbes of diabetic mice.Richness and diversity.?The relative abundance of Verrucomicrobiae(family)Bacteroides(genus),Akkermansia(genus),Lachnoclostridium(genus),Akkermansia_muciniphila(species)in the DBHR group was significantly higher than that in the DB group.The relative abundance of these flora and blood glucose values were significantly negatively correlated,which may be an important flora for the regulation of Coptis chinensis and ginseng medicine.Among them,Akkermansia_muciniphila plays a key role in reducing the inflammatory response,so it may be the key strain of Coptis chinensis and ginseng medicine to regulate intestinal flora to reduce blood sugar.conclusion1.The method of clearing away heat and benefiting Qi of diabetes is the basic thinking of Professor Lu Renhe and Professor Zhao Jinxi in treating diabetes.Coptis chinensis and ginseng are not only the representative drugs of heat clearing and qi benefiting drugs,but also the common drugs for the treatment of type 2 diabetes.They are found to have obvious correlation in the clinical case mining,so they can be used as the representative drugs for the treatment of heat clearing and qi benefiting.2.Through the analysis of network pharmacology,it is found that quercetin,berberine,kaempferol,arachidonic acid,ferulic acid,stigmasterol and so on are the main active components of Coptis chinensis and Panax ginseng,which may be the important compounds in the "drug pair" of Coptis chinensis and Panax ginseng.Coptis chinensis and Panax ginseng are the core targets for the treatment of type 2 diabetes,which are related to drug metabolism,insulin resistance and inflammatory response.They also participate in AMPK signal pathway,NF-?B signal pathway and glucagon signal pathway.TNF and IL1B,the targets of inflammatory factors,are enriched in NF-?B signaling pathway.3.Through animal experiments,it was found that Coptis and ginseng could significantly reduce the blood glucose,the content of serum LPS,the expression of IL-1? in pancreatic tissue and p-NF-?B p65/NF-?B p65 in liver tissue.The anti-inflammatory mechanism of its treatment for type 2 diabetes may be related to the regulation of intestinal flora disorder and the inhibition of NF-?B inflammatory factor pathway activation caused by the increase of LPS.The relative abundance of Verrucomicrobiae(family)Bacteroides(genus),Akkermansia(genus),Lachnoclostridium(genus),Akkermansia_muciniphila(species)in the DBHR group was significantly higher than that in the DB group.These groups may be important for the regulation of Coptis chinensis and Panax ginseng.Akkermansia_muciniphila plays a key role in reducing the inflammatory response,so it may be the key strain of Coptis chinensis and Panax ginseng drug pair for regulating intestinal flora to regulate glucose metabolism.