Professor Guo Shuwen's Research On Medication Rule And Network Pharmacology In The Treatment Of Stable Angina Pectoris Of Coronary Heart Disease

Objective:To study Professor Guo Shuwen’s traditional Chinese medicine prescription for stable angina pectoris of coronary heart disease by using the traditional Chinese medicine inheritance support system(TCMISS),and summarize the medication rule of Professor Guo Shuwen.At the same time,use the network pharmacology analysis to study the core drugs which are from the TCMISS,explore its action mechanism and provide some data support for clinical rational drug use and new drug development.Methods:1.The case data of Professor Guo Shuwen who treated patients in the National Medical Hall from May 2015 to May 2020 was screened according to the inclusion and exclusion criteria.The selected cases were preprocessed and inputted into the TCMISS.Constantly improve the background database according to the situation,and use the systematic statistical reports and data analysis module for correlation analysis and cluster analysis to derive the research results.2.The core drugs was studied by the network pharmacology.The chemical composition and protein targets of core drugs were screened by traditional Chinese medicine system pharmacology database and analysis platform(TCMSP).The related targets of coronary heart disease with stable angina pectoris were screened by GeneCards database,OMIM database,DrugBank database and TTD database.The above protein targets were standardized by Uniprot protein database.The drug action target and the disease target are intersected,and the intersection target is introduced into the STRING 11.0 platform to construct the target protein interaction(PPI)network.The drug and disease targets are analyzed by GO enrichment analysis and KEGG pathway analysis.The related network is constructed by Cytoscape3.7.1,and the effective components,action targets and biological pathways of drugs are screened.Results:1.Gender and age analysis showed that the male-to-female ratio was 1.41.The age of the patients is mainly distributed between 50 and 70,and the patients over 40 years old account for 90%of the total.Syndrome statistics show that the cases are mainly concentrated in the type of qi deficiency and blood stasis,the type of deficiency of both qi and yin and the type of deficiency of heart and kidney yang.2.Drug frequency analysis showed that the frequency of use from high to low were Radix Astragali,Hawthorn,Angelica sinensis,keel,oyster,Poria,Ligusticum chuanxiong,Bupleurum,Ophiopogon,Dilong and so on.3.Pharmacodynamic statistics showed that the overall drugs were mainly concentrated in tonifying deficiency drugs,activating blood circulation and removing blood stasis drugs,calming nerves,clearing heat drugs,calming liver and relieving wind drugs,relieving table drugs,antidietotic drugs,dietotic drugs,regulating qi drugs and expectorant antitussive and asthma drugs.4.The statistical analysis of four qi shows that Professor Guo Shuwen mainly uses warm medicine and cold medicine;among the five flavors,sweet medicine,bitter medicine and pungent medicine are mainly used,and the meridians are liver meridian,spleen meridian,heart meridian,stomach meridian,lung meridian,kidney meridian and so on.5.Based on the analysis of association rules,when the support degree is 90 and the Confidence level is 0.8,the combinations of(1)astragalus-Hawthorn,(2)keel-oyster,(3)a stragalus-angelica,(4)angelica-Hawthorn,(5)astragalus-keel,(6)astragalus-keel-oyster,(7)astragal us-oyster,(8)astragalus-angelica-Hawthorn,(9)Hawthorn-keel-oyster,(10)Hawthorn-oyster were obtained.Through the comparison of different degrees of support,we found that the drug gradually gathered to "Astragalus-Angelica-Chuanxiong-Poria-keel-oyster-Hawthorn",and got Professor Guo Shuwen’s core drug for the treatment of this disease,which was named "Yangxin Tongluo Anshen prescription".6.Based on the improved mutual information method,when the correlation degree is 8 and the punishment degree is 2,according to the correlation coefficient from hig h to low,the order is(1)Angelica-lichen,(2)Angelica-ballonflower,(3)safflower-arborvitae seed,(4)rhizoma cimicifugae-chuanxiong,(5)Radix Ophiopogonis-Semen Persicae,(6)Semen Persicae-arborvitae seed,(7)Semen Persicae-stir-fried white atractylodes,(8)radix Bupleuri-r hizoma Anemarrhenae,(9)radix Bupleuri-stir-fried white atractylodes,(10)rhizoma cimicifuga e-radix Bupleuri,etc.Based on the correlation coefficient,32 drug combinations and 16 new prescriptions were obtained by entropy cluster analysis of complex system.7.There are 10 active components in Ligusticum chuanxiong,5 active components in Angelica sinensis,21 active components in Radix Astragali,14 active components in Poria,6 active components in Hawthorn,2 active components in keel and 2 active components in oysters.There are 54 active components and 692 action targets in Yangxin Tongluo Anshen recipe.8.A total of 1006 targets related to coronary heart disease with stable angina pectoris were obtained,and a total of 215 potential targets were obtained after intersecting with drug targets.9.A total of 2858 items were obtained by go enrichment analysis,including 210molecular functions,2507 biological processes and 141 cellular components.A total of 369 biological pathways were obtained by KEGG pathway analysis.Finally,the main pathways of Yangxin Tongluo Anshen recipe in treating stable angina pectoris of coronary heart disease were AGE-RAGE signal pathway,cGMP-PKG signal pathway,NF-kB signal pathway,Wnt signal pathway and PPAR signal pathway.Conclusion:1.Professor Guo Shuwen’s core medicine for the treatment of stable angina pectoris of coronary heart disease is Yangxin Tongluo Anshen Formula,Radix Astragali-Angelica Nourishing Heart,Chuanxiong-Hawthorn promoting Blood Circulation and dredging collaterals,keel-Oyster to calm the mind.Guo Shuwen always seize the basic pathogenesis of"deficiency and solid",and pay attention to the integration of form and spirit and the harmony of mind and mind.Drugs often enter the liver meridian,attach importance to viscera,meridians and collaterals,and treat them as a whole.Guo Shuwen is good at grasping medicinal properties and using both cold and warm.2.In this study,the mechanism of Yangxin Tongluo Anshen recipe on stable angina pectoris of coronary heart disease was studied by the method of network pharmacology.the results showed that Yangxin Tongluo Anshen recipe intervened and regulated coronary heart disease stable angina pectoris through multi-component,multi-target and multi-pathway system.The main chemical components selected were beer sterol,gingerin,isorhamnetin,chrysanthemic acid C,metianine and dihydroisoflavone.The core targets are AR,ESR2,PTGS1,ESR1,ALOX5,NOS2,PPARG and PTGS2.Yangxin Tongluo Anshen recipe treats stable angina pectoris of coronary heart disease through antioxidant stress,inhibition of inflammation,inhibition of platelet aggregation,improvement of lipid metabolism and slow down of atherosclerosis.