| Background:Hyperlipidemia(HLP)is a metabolic disease,endangering the arteries,heart,brain and other parts,is one of the main risk factors of atherosclerosis and coronary artery disease,and also increases the risk of stroke,diabetes,fatty liver and other diseases.Taking effective treatment measures can prevent the further development of the disease,reduce the incidence and mortality of cardiovascular diseases,and improve the quality of life of patients.According to traditional Chinese medicine,the etiology and pathogenesis of hyperlipidemia is mainly due to the deficiency of the essence and the deficiency of the original condition,and the disease is mainly located in the spleen.The spleen is the source of qi and blood biochemistry,and if the spleen qi is weak,the qi of the whole body is weak."Qi is the commander of blood",if qi deficiency cannot promote blood circulation,blood stasis is easy to form.The spleen governs the movement and transformation,and the deficiency of the spleen cannot move the water and valley,it will condense into the evil of phlegm.Therefore,turbid phlegm and blood stasis are the pathological products of hyperlipidemia.Sanwei Qingzhi formula is a clinical experience formula from TCM experts,which is composed of Radix Paeoniae Rubra,Fructus aurantii Immaturus and Allium macrostemon.Basic research shows that Sanwei Qingzhi decoction has certain curative effect on hyperlipidemia.Objective:The method of network pharmacology is used to construct the biological network of Sanwei Qingzhi Decoction in the treatment of HLP,analyze the effective target of Sanwei Qingzhi Decoction in the treatment of HLP,explore its mechanism of action in the treatment of HLP,and provide a theoretical basis for clinical treatment.Carry out exploratory clinical trials to verify the feasibility of the test plan,preliminarily evaluate the efficacy and safety of Sanwei Qingzhi Decoction in the treatment of HLP(phlegm and blood stasis),and discuss the key points of quality control in clinical research on hyperlipidemia,which are confirmatory Research and development provide basic data and quality control recommendations.Put forward some suggestions for the quality control points of clinical research on hyperlipidemia.Methods:1.This survey aims to select the effective component of Sanwei Qingzhi Decoction which consists of Red peony root,Fructus Aurantii and Xeibai)and to make target prediction for it.Under the conditions of OB >30% and DL>0.18,the effective active ingredients of Sanwei Qingzhi Decoction were screened out from TCMSP database,Then it becomes accessible to take target prediction.The disease targets of HLP were selected from Gene Cards database,NCBI gene database and OMIM database.Cytoscape software was used to construct the target network of effective active ingredients of Sanwei Qingzhi Decoction in the treatment of HLP,And the GO Ontology(GO annotation)and KEGG pathway analysis of the target were carried out by String database.2.There are 60 patients among healthy testing population which select from Ningjin Hospital located in Hebei province.The Subjects has signed the informed consent form before they take part in it.The subjects were divided into trial group and the control group through SAS software that generate random sequence.Each group has 30 cases in this survey.The subjects in experimental group take oral Sanwei Qingzhi Decoction granules,And the subjects in control group take oral Sanwei Qingzhi Decoction granules of mimetics,twice a day,the course of 8 weeks.Low density lipoprotein(LDL),triglyceride(TG),total cholesterol(TC),high density lipoprotein(HDL)levels and TCM syndrome scale scores were compared between the two groups before and after treatment,and adverse events were recorded.3.Objective to construct the target network diagram of Sanwei Qingzhi Decoction in the treatment of hyperlipidemia by using Cytoscape software,and analyze the target with go Ontology(GO annotation)and KEGG pathway through string database.Results:1.In the TCMSP database,29 components and 88 targets of red peony were obtained;5 components and 88 targets of Fructus Aurantii;11 components and 192 targets of Fructus Aurantii.Through Gene Cards database,NCBI gene database,OMIM database to search for HLP disease targets,1378 HLP-related genes were obtained.Using Venn diagrams to intersect drug targets and disease targets,122 targets were obtained.Use the String database to do GO annotation and KEGG pathway analysis on 122 targets.The age signaling pathways of diabetes complications,Kaposi’s sarcoma-related herpes virus infection,fluid shear stress and atherosclerosis are the top signaling pathways.2.After taking the medicine for 4 weeks,the effective rate of low-density lipoprotein reduction in the test group was24.0%(6/25),and the effective rate in the control group was 22.2%(6/27).The test group was higher than the control group,P> 0.05.After taking the medicine for 8 weeks,the effective rate of decrease in the experimental group was 17.4%(4/23),and the effective rate of decrease in the control group was 16.0%(4/25).The experimental group was also higher than the control group,P>0.05.After taking the drug for 4 weeks,the effective rate of triglyceride reduction in the test group was 52.0%(13/25),and the effective rate of triglyceride reduction in the control group was 44.4%(12/27).The test group was higher than the control group,P>0.05.After taking the drug for 8 weeks,the effective rate of decrease in the experimental group was 43.5%(10/23),and the effective rate of decrease in the control group was 36.0%(9/25),the experimental group was also higher than the control group,P> 0.05.After taking the medicine for 4 weeks,the effective rate of reducing total cholesterol in the test group was20.0%(5/25),and the effective rate of reducing the total cholesterol in the control group was22.2%(6/27),P> 0.05.After taking the medicine for 8 weeks,the effective rate of decrease in the experimental group was 17.4%(4/23),and the effective rate of decrease in the control group was 12.0%(3/25).The experimental group was higher than the control group,P>0.05.After taking the medicine for 8 weeks,the scores of TCM phlegm turbidity and blood stasis syndrome of the experimental group decreased.In terms of safety,9 subjects in the test group had symptoms such as insomnia and abdominal distension,and 7 subjects in the control group had adverse reactions such as head swelling.3.The process of trial quality management in this exploratory study was analyzed and summarized from the aspects of study design,investigator quality control,and subject compliance control,etc.,so as to provide reference for the design,implementation and quality control of later deterministic clinical trials.Conclusion:Sanwei Qingzhi recipe regulates blood lipid by acting on AKT1,IL6,VEGFA and other targets,regulating HIF-1,AGE-RAGE,IL-17 and other signaling pathways,which provides a theoretical basis for the clinical use of Sanwei Qingzhi recipe in the treatment of HLP.The results of exploratory randomized controlled trial showed that Sanwei Qingzhi decoction could improve the levels of low density lipoprotein,triglyceride,total cholesterol and phlegm turbid blood stasis syndrome in patients with hyperlipidemia.Considering the limitations of this study,we still need to carry out a larger sample size of multi center randomized controlled clinical trials to further verify the clinical efficacy of Sanwei Qingzhi Decoction in the treatment of HLP(phlegm and blood stasis syndrome). |
PDF Full Text Request