Clinical And Related Basic Research On The Treatment Of Impaired Glucose Regulation With Metabolic Syndrome By The Traditional Chinese Medicine Compound Yitangkang

Purpose:1.To observe the clinical effect of Yitangkang combined with basic treatment on impaired glucose regulation and metabolic syndrome and its influence on blood sugar,blood lipid,blood pressure,BMI,waist circumference,TCM syndromes,symptoms and quality of life scores,and to make stratified analysis from age,gender and waist circumference in order to find the best suitable population.2.To evaluate the pharmacodynamics of Yitangkang in vitro and explore its possible mechanism from the perspective of PI3K/AKT insulin signaling pathway.3.Based on the data mining technology and relying on the TCM inheritance assistant platform,the medication rule and syndrome type characteristics of the Trinity application theoretical framework of diabetes mellitus are excavated,and the"prescription of traditional Chinese medicine"provides a new direction for clinical treatment at the same time.Methods:1.Paper One:Clinical study,collected 165 patients with impaired glucose regulation and metabolic syndrome（phlegm-heat junction type）.According to the principle of randomization,the patients were divided into control group（83 cases）and treatment group（82 cases）.Both groups were treated with basic Western medicine.The treatment group was treated with Yitangkang on this basis,while the control group was treated with placebo for 12 weeks.To observe the changes of clinical efficacy,blood sugar,blood lipid,blood pressure,BMI,TCM syndromes,symptoms,quality of life scores and other indicators;to analyze the changes of blood sugar,blood lipid,blood pressure,BMI and other indicators in different stratification by age,sex and waist circumference.2.Paper Two:In the experimental study,a stable and reliable IR-HepG2 cell model was established by 24 hours stimulation with high insulin(1×10^-6mol/L).Yitangkang high,medium,low,blank serum and metformin serum interfered with IR-HepG2 cells respectively.Glucose consumption of IR-HepG2 cells was measured by glucose-peroxidase method;cell activity was measured by MTT method;and Yitangkang was determined by Annexin V-FITC/PI method.The effects of drug-containing serum on apoptosis of IR-HepG2 cells were studied.The expressions of IRS-2,PI3K and AKT in IR-HepG2 cells were detected by RT-PCR,and the expressions of IRS-2 and AKT phosphorylated protein in IR-HepG2 cells were detected by Western blot.Paper Three:Literature research,using the traditional Chinese Medicine Inheritance assistant platform to extract and sort out the ontology clauses related to syndromes and prescriptions in the theoretical framework of diabetes,and establish a database.Data mining is carried out by using unsupervised data mining methods such as integrated improved mutual information method,complex system entropy clustering,unsupervised entropy hierarchical clustering,and so on.Results:Paper One:1.There was no significant difference in baseline between the two groups before treatment,which was comparable（P>0.05）.2.Comparing the effective indexes of the two groups before and after treatment,the control group could significantly reduce 2hPG,BMI and blood pressure（P<0.01）.The treatment group can not only improve 2 hPG,BMI and blood pressure,but also FPG,TG,HDL-C,LDL-C and waist circumference.Compared with the control group,the treatment group can improve 2 hPG,TG,BMI,blood pressure and waist circumference better than the control group.3.In the treatment group,the total FPG,2H PG,LDL-C,BMI,blood pressure and waist circumference were reduced by 53.66%,60.98%,52.44%,30.49%,89.02%and58.54%,respectively,with significant difference compared with the control group（P<0.05）.4.The scores of syndromes,symptoms and quality of life in both groups decreased（P<0.05）,and the difference was significant（P<0.05）.5.Achievement rate of TCM syndrome integral was 84.15%in the treatment group,60.24%in the control group,80.49%in the TCM symptom integral,51.81%in the control group,73.17%in the quality of life integral and 45.78%in the control group.There was a significant difference between the two groups（P<0.05）.6.According to age stratification analysis,the decrease of 2hPG in the control group was mainly manifested in people aged 20-59;the decrease of systolic blood pressure was mainly manifested in people over 40 years old;the decrease of diastolic blood pressure was confined to people aged 40-59 years;and the BMI of all age groups was significantly reduced.The control group had no obvious therapeutic effect on FPG and LDL-C in general,but stratified results showed that basic treatment could reduce FPG and LDL-C in 20-39 years old population（P<0.05）.Yitangkang can reduce2hPG of 40-59 years old,BMI of 20-39 years old,systolic blood pressure of 20-59years old and diastolic blood pressure of people over 40 years old.Yitangkang has no obvious therapeutic effect after stratification although it reduces TG as a whole;it is ineffective on fasting blood sugar as a whole,but it has a decreasing effect in people aged 40-59.7.Gender stratification analysis showed that the reduction of 2hPG in basic treatment was mainly in women,and there was no gender difference in blood pressure and BMI.After treatment,Yitangkang decreased 2 hPG and BMI（P<0.01）,especially in male patients.There was no difference between men and women in improving blood pressure.Although FPG did not decrease in general,there was a difference between men and women after stratification,that is,it mainly decreased in men.8.By waist circumference stratification analysis,the control group improved blood pressure and BMI of patients with phlegm-heat junction.Reducing 2hPG and HBA1C was mainly effective for female patients,whether waist circumference was abnormal or not,and also could reduce 2hPG of men with abnormal waist circumference.The decrease of LDL-C and TG was mainly manifested in male patients with normal waist circumference and abnormal waist circumference;the increase of HDL-C was mainly manifested in female patients with normal waist circumference;the effect on FPG was not effective for male patients with abnormal waist circumference,but also for other three groups.Yitangkang can improve blood pressure and BMI in all population.The decrease of 2hPG in male patients was significant（both normal and abnormal waist circumference groups were acceptable）,and the decrease of TG in female patients with normal waist circumference was significant（P<0.01）.Although Yitangkang had no significant improvement on FPG,HDL-C,LDL-C and HBA1C in general,it was found that Yitangkang could reduce FPG,HBA1C and LDL-C in men and women with abnormal waist circumference,decrease FPG level in men with normal waist circumference and HBA1C level in women with normal waist circumference,and increase HDL-C level only in women with abnormal waist circumference.Paper Two:1.After 24 hours of insulin exposure,the glucose consumption reached the lowest level and had no effect on cell viability.IR-HepG2 cells could be established and the cell model was stable within 48 hours.2.When 15%Yitangkang serum acts on IR-HepG2 for 48h,the consumption of glucose reaches the maximum,and has no effect on cell activity.The serum concentration and action time will be used for subsequent experiments.3.Compared with the control group,apoptotic cells occurred in the model group and Yitangkang group,and the difference was significant（P<0.01）.Compared with the model group,Yitangkang containing serum could reduce the apoptotic rate and inhibit the apoptosis,the apoptotic rate was 11.2%and 7.6%respectively.4.Compared with the control group,the expression of IRS-2,PI3K and AKT in the model group decreased significantly（P<0.01）.After treatment with Yitangkang,the expression of IRS-2,PI3K and AKt in the IR-HepG2 cells increased compared with the model group（P<0.01）.5.Compared with the control group,the expression of IRS-2 protein and p-AKT protein in the model group decreased（P<0.01）.After treatment with Yitangkang containing serum,the expression of IRS-2 protein and p-AKT protein increased compared with the model group（P<0.01）.Paper Three:1.Based on 630 selected ontology clauses,drug frequency analysis shows that there are 351 herbal medicines in 630 ontology clauses,among which the highest frequency is 220 times,the lowest frequency is 1 time,and the total frequency is more than 50times.The top five flavors are licorice,ginseng,Poria cocos,ophiopogon,Coptis chinensis.2.According to the Apricxri algorithm of association rules,the core drug combinations for diabetes were extracted.Through the analysis of"prescription rules",29association rules and 69 drug combinations patterns were obtained.The first five patterns were"ginseng-licorice","Ophiopogon-ginseng","Ginseng-Poria","Ophiopogon-Hangdi","Ophiopogon-tianhua"according to the frequency of drug combinations."3.According to the data mining method of complex system entropy clustering,hierarchical clustering analysis was carried out,and 10 core drug combinations were obtained.Five new prescriptions were obtained by unsupervised entropy hierarchical cluster analysis on the basis of core drug combination extraction.4.Systematic meridian analysis was made on 630 articles,involving 12 meridians.The first six meridians were lung meridian>spleen meridian>stomach meridian>Heart Meridian>kidney meridian>liver meridian,and the lowest frequencies were small intestine meridian（148）,pericardium meridian（44）,and three Jiao meridian（31）.5.The system carries on the analysis of four scents and five flavors of medicines in the ontology clause database.Among the five flavors,sweet medicines are the most frequently used,followed by bitter and spicy ones.Among the four gases,cold and warm medicines were the most frequently used,while cold medicines were the least frequently used.6.According to the database,a total of 90 syndromes were excavated,of which the deficiency of true yin,deficiency of yin,dryness-heat and stomach-heat syndrome ranked the top three,far higher than other syndromes.Conclusion:Paper One:1.Traditional Chinese medicine Yitangkang combined with basic treatment can effectively reduce blood sugar,blood pressure and BMI of impaired glucose regulation and metabolic syndrome（phlegm-heat syndrome）.It can also improve blood lipid and waist circumference.2.Yitangkang can improve the clinical symptoms and quality of life of patients.3.Under the stratification of age,sex and waist circumference,Yitangkang,a traditional Chinese medicine compound,has refined the treatment population and further improved its precise adaptation to the population.Paper Two:1.A stable IR-HepG2 cell model could be established by insulin concentration of 1×10^-6 mol/L for 24 hours,and the cell model could be stable for 48 hours.2.15%Yitangkang drug-containing serum can maximize the consumption of IR-HepG2 glucose for 48 hours.Its mechanism may be related to the up-regulation of key genes and protein expression in PI3K/AKT signaling pathway.3.Yitangkang drug-containing serum can inhibit IR-HepG2 apoptosis,reduce cell damage and protect cells.Paper Three:1.Based on the application theory of diabetes in ancient books,prescriptions are flexible,and the main drugs are tonifying qi,invigorating spleen and clearing heat and nourishing yin.2.The medication rule of"prescription of medicine and syndrome"confirms Yitangkang’s therapeutical method and professor Shi Yan’s academic thought of"treating from spleen".