Study On Mechanism Of Damingying Ⅱ In The Treatment Of Diabetic Macular Edema Based On Date Mining And Pharmacodynamics

Objective:The traditional Chinese medicine inheritanc eassistance system(V2.5)was used to summarize the prescription rules of Professor Sun He in drug therapy of diabetic macular edema.To predict the possible effective targets and pathways of DMY Ⅱ in the drug therapy of diabetic macular edema by network pharmacology study.DMY Ⅱ decoction-containing serum was used to interfere with HRMECs after the dysfunction.Through the detection of cell proliferation activity,VEGF and claudin-5 expression,the mechanism of DMY Ⅱ prescription protecting blood-retina barrier was explored,and it provided the experimental basis for clinical therapy.Method:The first part : the medical records of Professor Sun’s treatment of diabetic macular edema in recent 10 years were collected,and 197 prescriptions were selected as research objects.The prescriptions in the medical records were sorted out,and the Excel database was established and then imported into the system.we performed frequency statistical analysisassociation,rule analysis and cluster analysis on the data platform in order to explore Professor Sun prescribing rules and treatment experience in the management of diabetic macular edema.The second part: the traditional Chinese medicine System pharmacological database and analysis platform were used to screen the active ingredients and potential targets of various traditional Chinese medicines in DMY Ⅱ prescription.DME-related genes were excavated from Genecards and OMIM databases,and the interaction network diagram of drug-component-disease was constructed.A bioinformatic database(Metascape)was used to perform GO biological process enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis for both drugs and targets of disease,in order to explore potential effective targets and pathways of DMY Ⅱ in the treatment of diabetic macular edema.The third part: the model of retinal endothelial cell dysfunction under high glucose was established,and the serum containing DMY Ⅱ was used to intervene the dysfunction of retinal endothelial cells.By detecting cell proliferative activity,VEGF and claudin-5 expression,the mechanism of protecting blood-retina barrier by DMY Ⅱ prescription was explored,which could afford experimental data for clinical treatment.RESULT:The first part :The results showed that there were 17 medicinal materials with more than 50 usages of TCM,among which the five medicinal materials with the highest frequency were Fuling,Gouqizi,Gegeng,Wuweizi and Shengdihuang.The second part : the top active ingredients of DMY Ⅱ were Schisandrin,berberine,lycium barbarum polysaccharide.The top ranked proteins by Degree were SR1,KDR,SRC and CDK2.The results showed that the top of the KEGG enrichment list were AGE-RAGE signaling pathway,PI3K-Akt signaling pathway,MAPK signaling pathway,etc.The third part :1.High glucose(25mmol/L)can promote the proliferation of human retinal vascular endothelial cells,which can establish a stable high glucose HRMECs cell injury experimental model.2.The high-dose serum containing of DMY Ⅱ significantly inhibited the proliferation of HRMECsunder high glucose(P < 0.05).3.The relative expression level of VEGF was significantly decreased in the low-dose serum containing of DMY Ⅱ group(P < 0.05).4.The relative expression level of claudin-5 was significantly increased in the high-dose serum containing of DMY Ⅱ group,and the difference was statistically significant compared with model group(P < 0.05).Conclusion:1.In the treatment of diabetic macular edema,Professor Sun mainly focuses on tonify qi and induce diuresis,enrich yin and cool blood,and activate blood and resolve stasis,and concentrates on regulating the function of zang fu organs with flexible prescription.2.The main active ingredients of DMY Ⅱ act on different targets,treating diabetic macular edema through different therapeutic aspects such as circulation,metabolism,anti-inflammatory and antioxidant,etc.The regulation of signal pathways such as AGE-RAGE,PI3K-Akt and MAPK may be the mechanism of action of DMY Ⅱ in treating diabetic macular edema.3.The DMY Ⅱ can interfere with DME by inhibiting the abnormal proliferation of HRMECs which caused by high glucose environment.By reducing the expression of VEGF factor and increasing the expression of claudin-5,the DMY Ⅱ can protect the blood-retinal barrier and reduce the leakage of retinal microvessels,and treat diabetic macular edema.