Study On The Mechanism Of Real-World Core Prescription For Hypertensive Renal Damage Based On Network Pharmacology

Objective:The herbs for the treatment of hypertensive renal damage in the real world was analyzed by network pharmacology.The effective prescription of traditional Chinese medicine was screened and explored Its mechanism was explored and analyzed,and a model was established in spontaneously hypertensive rats to verify the efficacy and mechanism of the prescription.Methods:1.Obtaining the core prescription for the treatment of hypertensive renal damage:extract the electronic medical records of hypertensive renal damage in the affiliated Hospital of Shandong University of traditional Chinese Medicine from July 2014 to May 2017.Using hierarchical network extraction,BGLL and other algorithms to mine the core combination of traditional Chinese medicine and patients’ symptoms and signs in the electronic medical records.Using the public database to establish a network of protein interaction between traditional Chinese medicine and disease.The KNN model was used to analyze the clinical and biological characteristic information,to determine the effective compounds of traditional Chinese medicine for hypertensive renal damage,and to determine the effective treatment prescription"Gao Shen Formula "combined with hierarchical clustering.In order to verify the effectiveness of the model,compare the KNN model with the classical models,and conduct a retrospective cohort verification of Gao Shen Formula;finally,analyze the pathway enrichment of Gao Shen Formula,and analyze its action mechanism from the target and pathway level.2.Animal experiment to verify the curative effect of Gao Shen Formula:spontaneously hypertensive rats were used to establish a model,and Wistar Kyoto rats were divided intoGao Shen Formula group,irbesartan group,model group and control group.The blood pressure was observed for 8 weeks.Renal pathological changes were observed by renal HE staining,serum TNF-α levels were measured by Elisa kit,and the expression of NF-κB p65 and phosphorylated p65 in kidney was detected by Western Blot.Results:1.A total of 14 core combinations of traditional Chinese medicine and 5 symptom and sign communities were obtained from the real-world data.A total of 76 effective compounds were obtained by using KNN model.After hierarchical clustering,Salvia miltiorrhiza,Angelica sinensis,Codonopsis pilosula,Rhizoma Atractylodes,Pinellia ternata,Rhizoma Curcumae and licorice were determined as the "high kidney prescription".Compared with the classical model,the AUC value of KNN model was the best.Retrospective cohort verification showed that Gao Shen Formula could reduce serum creatinine and CKD stage[OR=2.561,95%CI(1.025-6.406),P<0.05].From the aspect of target and pathway enrichment,it is found that Gao Shen Formula can regulate the inflammation-related pathways dominated by NF-κB signal pathway by acting on the activities of inflammatory factors such as TNF-α receptor,IL-1β and IL-6,and affect the downstream glucose and lipid metabolism pathways by affecting INS,PPARG,VEGFA and other targets.It is speculated that the mechanism of Gao Shen Formula is to reduce the regulation of inflammatory reaction,inhibit the renal damage caused by excessive activation of reninangiotensin-aldosterone system,and regulate energy metabolism.2.In animal experiment,it was found that the blood pressure of spontaneously hypertensive rats decreased after the intervention of Gao Shen Formula(P<0.05),and the left ventricular myocardium was thinner than that of the model group(P<0.05),suggesting that Gao Shen Formula could improve left ventricular myocardial remodeling.In kidney aspect,the pathological sections of Gao Shen Formula group showed that the renal damage was slighter and the accumulation of inflammatory cells was less.At the same time,the expression of NF-κB p65 and its phosphorylated protein were lower in Gao Shen Formula group,indicating that NF-κB signal pathway was inhibited and the level of serum TNF-α receptor was lower,indicating that the inflammatory reaction of the body was lighter.Conclusion:In this study,network pharmacology is applied to real-world data analysis,which can integrate the biological characteristics of traditional Chinese medicine with clinical data,and can be used to discover the therapeutic prescription "Gao Shen Formula" for the treatment of hypertensive renal damage.after network pharmacology analysis and animal experiments,it is found that Gao Shen Formula can alleviate inflammatory reaction,reduce kidney disease,reduce blood pressure,improve myocardial remodeling by inhibiting the relevant inflammatory pathway with NF-κB signal pathway as the core.