Biological Mechanism Of Traditional Chinese Medicine Based On Network Module To Interfere With Diabetic Microvascular Complications In Homotherapy For Heteropathy

Background:Diabetic microangiopathy(DM)includes Diabetic retinopathy(DR),Diabetic peripheral neuropathy(DPN),Diabetic nephropathy(DKD),and is one of the leading causes of death and disability in diabetes.The extensiveness of the site of change,the incidence of concealment,often involves the entire body of different organs and different physiological and pathological systems.Clinical treatment also belongs to different clinical sub-specialty,having their own special characteristics.Because of this,many clinicians have neglected their co-existence of the physiological and pathological basis,lack of effective co-morbid treatment strategies and a holistic view of treatment.In modern medicine,these three diseases are intrinsically linked in physiology and pathology.In traditional Chinese medicine,"same disease treatment" has been guiding the clinical practice of traditional Chinese medicine since ancient times and is an important part of syndrome differentiation and treatment.Chinese medicine has been used for the treatment of diabetes for thousands of years.In recent years,with the emergence of emerging disciplines such as systems biology,network pharmacology,and bioinformatics,multidisciplinary research systems have gradually emerged in the prevention and treatment of complex diseases by Chinese medicine.Now science and technology to explore the biological mechanism of Chinese medicine compound intervention complex diseases that has become a feasible means.In order to further explore the mechanism of traditional Chinese medicine interfering in the pathogenesis of diabetic microvascular complications,we took Professor Xiaolin's experience Tang-Bi-fang as an example to explore the effects of muti-targets in order to explore the role of Chinese medicine in interfering with diabetic microvascular "different diseases".Objects:1.Using network modularity to analyze three complications of diabetic nephropathy,diabetic peripheral neuropathy,and diabetic retinopathy,constructing a genetic integration network of three diseases and identifying functional modules and enrich relevant biological functions and signal pathways to reveal traditional Chinese medicine The biological mechanism under the theory of"same treatment for different diseases and diseases".2.Using network pharmacology in combination with bioinformatics to analyze the biological mechanisms of Professor Tong Xiaolin's experience Tang bi fang in treating diabetic nephropathy,diabetic retinopathy,and diabetic peripheral neuropathy,and further revealing the therapeutic effects of Chinese medicine on diabetic microvascular complications Biological mechanism.Methods:1.Using Agilent literature search software Diabetic nephropathy,diabetic peripheral neuropathy,diabetic retinopathy-related disease overlap and unique associated gene networks,and using Cytoscape software to visualize the data network processing,analyze the topological properties of the gene network,including clustering Coefficients,number of nodes,network diameter,network centricity,network radius,etc.The MCODE cluster analysis method is used to identify the modules and analyze the attributes of their modules to obtain a more stable module network.Using the 6.8 version of the DAVID software,the module was subjected to biological function enrichment analysis.Human genome data was used as a reference background.The Functional Annotation Chart function was used to screen the corresponding GO(Gene Ontology)biological function and KEGG with P value less than 0.01.(Kyoto Encyclopedia of Genes and Genomes)Signaling Pathways,and based on overlapping and unique genes,search for genes-related Chinese medicine in the PubMed database,'calculate correlation coefficients,and determine the most relevant Chinese medicine for the disease.2.Use TCMSP database to screen out the effective components and related target proteins in glycosides,use the network Cytoscape 3.2.1 to construct glycosides-target interaction network and use Bisogenet plug-in to construct sugars.The active ingredient of the target-the target PPI interaction network;the genetic data of diabetic nephropathy,diabetic peripheral neuropathy,and diabetic retinopathy,as well as related targets,were found through the Mendelian genetic database OMIM and the GAD database,and a role network was constructed using cytosape.,and the use of Bisogent to construct a PPI network between diseases;merge the two PPI networks and perform topological screening on the core targets.KEGG with the David database Functional enrichment analysis of pathways and biological processes of GO to study the mechanism and principles of Tangbi decoction in the treatment of diabetic microvascular vascular complications.Results:1.Obtain a network of three disease overlapping genes and their own unique genes,respectively.The network of DR-related genes includes 159 nodes at 489 edges,the DKD-associated gene network contains 271 nodes and 985 edges,and the DPN-related gene network contains 381 nodes and 871 edges.The module was calculated after the MCODE software,including 126 modules for diabetic nephropathy,98 modules for diabetic retinopathy,72 modules for diabetic peripheral neuropathy,and 9 overlapping modules for DKD and DR network modules.There are 29 biofunctional annotations,7 reaction processes,6 metabolic processes,5 biosynthesis,4 glycosylation,2 oxidation processes and autophagy,development process,pathway,transport process and phosphorylation process,among them Four pathway pathways were identified,including glycosylation,biosynthesis,lysosomes,and phosphorylation pathways.DKD and DPN have 5 overlapping modules.Including 20 biofunctional annotations,of the 8 metabolic processes,5 were biosynthetic 1 glycosylation,1 autophagy,l hormone level regulation response process,12 common pathways were identified including 8 metabolic processes s 2 biosynthesis,2 synthesis and metabolic processes,1 lysosome and 1 conversion pathway.DR and DPN have 40 overlapping modules.Of these 73 biological functions were annotated.Three pathways have been identified:cell cycle,DKDA replication,and sphintoglycolipid biosynthesis.DR,DKD,and DPN share three overlapping modules,including 5 in the biosynthetic process,4 glycosylation,3 metabolic processes,and 1 autophagy process.Two overlapping pathways were identified:lysosomes and glycosphingolipids.The PubMed database was used to search for overlapping genes and unique genes for the three diseases.Only AKR1B1 was found in overlapping genes.EPO was found in traditional Chinese medicines:Astragalus membranaceus,Angelica sinensis,Radix Astragali,and Safflower.The traditional Chinese medicines that have unique gene frequencies of more than 2 and that have the highest correlation coefficient with overlapping genes,such as:Huangqi,Artemisia annua,Salvia miltiorrhiza,Puhuang,Gujianyu,Panax notoginseng,Eucommia ulmoides,Chishao,Artemisia,Ephedra,Chuanxiong,Qing Artemisia,Millettia,Astragalus,Rhodiola,Tripterygium.Among them,purslane,Tripterygium wilfordii,and Artermisia annua are rarely used in TCM syndrome differentiation prescriptions.By searching the literature,it was found that extracts of purslane,tripterygium wilfordii,and artemisia annua can affect the angiotensin system,which has the effects of lowering blood glucose,blood lipids,and blood pressure,and also provides new ideas for clinical prescription drugs.2.Through a comprehensive search of several Chinese medicine chemical databases,a total of 88 chemical constituents of Astragalus membranaceus,107 constituents of Guizhi,78 components of Angelica,69 components of Millettia,and 190 components of Chuanxiong were collected.A total of 532 known chemical constituents were obtained after detoxification.OB?30%of 74 components were selected and DL?0.18.According to the corresponding target found,Astragalus contains 21 species,6 species of cassia,14 species of white peony,25 species of Millettia,and 8 species of Chuanxiong.568 corresponding target proteins were found.The components and chemical components that were screened were mapped to target proteins according to their interactions.The Cytoscape software was used to construct the sugar-target component-target network.There are 1178 edges in the network,which represent the interactions between components and targets.In the 190 nodes of the network,there are 72 representative components.According to the targets corresponding to 72 components,a component target PPI network is constructed to construct component target PPI networks,including 2392 nodes,56277 edges,in OMIM,GAD There are 275 targets for diabetic peripheral neuropathy,diabetic retinopathy,and diabetic nephropathy found in the TTD database.According to the chemical composition of sugars and the direct target target interactions,there are 182 edges in the network representing disease targets.For point interactions,213 points represent the target protein node of the three microvascular complications.According to the target of 72 components and the corresponding three diseases,the target PPI network was constructed,including 1768 nodes and 23494 edges.Biologic and biologic pathway enrichment analysis was performed on 275 nodes of diabetes melliltus microvascular complications treated with glycosides.A total of 613 GO biologic processes were enriched,of which 394 had P values less than 0.01.There were 111 KEGG biologic pathways,86 of which P values less than 0.01,Conclusion:1.Through analysis of gene networks and module biological functions,diabetic nephropathy,diabetic retinopathy,and diabetic peripheral neuropathy were found.Their common pathological mechanisms are related to the processes of glycosphingolipid and lysosome biosynthesis,suggesting diabetic retinopathy and diabetes.There is a similar biological mechanism between peripheral neuropathy and diabetic nephropathy,and the Chinese side has demonstrated the theory of“same disease with different diseases”.Through literature analysis and traditional Chinese medicines with high complications genes,we discovered astragalus,artesunate,salvia miltiorrhiza puhuang,ghost arrow feather,panax notoginseng,eucommia bark,red peony root,wormwood,ephedra,chuanxiong,artesunate,Millettia,Astragalus,Rhodiola,Tripterygium.Among them,3 flavors of Chinese medicine,purslane,tripterygium wilfordii,and artesunate are not commonly used to treat diabetic microvascular complications,which may provide new ideas for the development of new clinical drugs.2.An online pharmacological analysis of Tangyinfang in the treatment of diabetic microvascular complications with "same treatment for different diseases and diseases",and an online pharmacological analysis of Tangyinfang for treatment of diabetic microvascular complications with "same treatment for different diseases",and speculated that glycosides can be used to inhibit nerves.The activation of JNK/SAPK signal pathway in the system stimulates peripheral nerve regeneration,and promotes the pre-effect of multi-target intervention by promoting epidermal growth factor,inhibiting inflammatory responses,reducing lipid metabolism disorders,regulating VEGF growth,and improving microvascular circulation.However,its application using network and software analysis to predict and analyze the mechanism of action of traditional Chinese medicine based on signaling pathway still has many theoretical defects,and more clinical trials and animal experiments are needed to further verify.