Clinical Research And Network Pharmacological Analysis Of Strengthening The Spleen And Removing Turbidity In The Treatment Of Atherosclerosis Based On Blood Turbidity Theory

Objective: By observing the clinical efficacy of modified Shuangyu Tiaozhi Decoction in the treatment of atherosclerosis(spleen deficiency and phlegm turbidity syndrome),we will evaluate the effectiveness and safety of the formula guided by the method of strengthening the spleen and removing turbidity.Based on network pharmacology,we will analyze the potential target of modified Shuangyu Tiaozhi Decoction in the treatment of atherosclerosis,as well as various biological processes,cell components,molecular functions and signal pathways that may be involved,so as to provide scientific basis and theoretical support for the clinical application and experimental research of method of strengthening the spleen and removing turbidity.Methods: Clinical study: 64 patients with atherosclerosis and syndrome differentiation of spleen deficiency and phlegm turbidity syndrome were collected in outpatient and ward,were randomly divided into treatment group and control group,with 32 cases in each group.Both groups were given routine treatment of basic diseases and oral treatment of rosuvastatin calcium tablets.At the same time,the treatment group was treated with modified Shuangyu Tiaozhi Decoction combined with western medicine,while the control group was treated with western medicine only.The course of treatment was 12 weeks.The changes of blood lipid content,serum high-sensitivity C-reactive protein(hs-CRP),carotid intima-media thickness(IMT),carotid intimal plaque area and curative effect of traditional Chinese medicine syndrome were evaluated before and after treatment.Network pharmacology research: search the effective active components of the drugs contained in modified Shuangyu Tiaozhi Decoction through TCMSP database,and predict the action target through Swiss Target Prediction database.Potential targets of atherosclerotic diseases were searched through Dis Ge Net,Gene Cards and Drug Bank databases.After the intersection of drugs and disease targets,the potential targets of drug-induced diseases can be obtained.Submitting these targets to the STRING platform can build a PPI network,analyze key targets and build a “herbs-components-disease-targets” network in Cytoscape software.Using “Bioconductor bioinformatics software package” in “R”language,GO enrichment analysis and KEGG enrichment analysis can be carried out on the network.Results: Clinical study: after 12 weeks of treatment,the blood lipid index,hs-CRP,carotid IMT,plaque area and TCM symptoms of the two groups were significantly improved after treatment(P<0.05),and the curative effect of the treatment group was better than that of the control group(P<0.05).Network pharmacology research: there are 917 potential targets in modified Shuangyu Tiaozhi decoction.After intersecting with 804 atherosclerosis related targets,118 co-acting targets were obtained.TNF,IL-1β,VEGFA,PPARγ and other key targets,which involves multiple biological processes such as inflammatory response,lipopolysaccharide response and sterol metabolism,as well as multiple signal pathways such as AGE-RAGE signal pathway,lipid and atherosclerosis and tumor necrosis factor signal pathway.Conclusion: The modified Shuangyu Tiaozhi Decoction guided by the method of strengthening the spleen and removing turbidity based on the theory of blood turbidity can effectively improve the lipid metabolism function of patients with atherosclerosis,with reducing the content of blood lipids,hs-CRP,the area of carotid IMT,plaque and score of clinical syndromes of traditional Chinese medicine.Modified Shuangyu Tiaozhi Decoction can regulate TNF,IL-1β,VEGFA,PPARγ and other key targets playing a role in the treatment of AS,which is related to AGE-RAGE signal pathway,lipid and atherosclerosis,tumor necrosis factor signal pathway and other signal pathways.