Meta-analysis And Network Pharmacology Research On The Treatment Of Vascular Dementia With Detoxification And Dredging Collaterals Based On The Theory Of Collateral Disease

Objective:1.To systematically evaluate the clinical efficacy and safety of Jiedu Tongluo method in the treatment of vascular cognitive impairment through meta-analysis,and analyze its influence on different outcome indicators,so as to provide reference for the research on the diagnosis and treatment of diseases with traditional Chinese medicine.2.To understand the clinical treatment of VD by Jiedu Tongluo method through data analysis,and summarize the prescription and types of Chinese medicine included in the literature,so as to provide reference for clinical diagnosis and treatment drugs.3.Through network pharmacology,core drug groups were screened and network construction was conducted to visually present the correlation between core drugs of detoxification and collateralization and VD,explore potential targets and pathways of action of detoxification and collateralization traditional Chinese medicine in the treatment of VD,and further clarify the mechanism of drug action.Method:1.Randomized controlled studies on the treatment of vascular dementia with detox and collateralization were searched from CNKI,Wanfang Database,Chongqing Weipu Full-text Database of Chinese Science and Technology Journals(VIP),Pub Med,Embase and Webof Science,and literatures meeting the requirements were screened according to inclusion and exclusion criteria.After literature quality assessment,Revman5.4 software was used to analyze the difference of efficacy among various indexes.2.TCM prescriptions included in the meta-analysis were input into Excel,drug frequency statistics were performed,and drug association rules were analyzed using SPSS Modeler 18.0.3.3.The TCMSP database was used to search for active ingredients and screen targets of calamus calamus,Astragalus membranaceus,ligusticum Chuanxiong and Rehmanniae radix radix.The targets were matched with corresponding genes.Meanwhile,VD related genes were searched in Gene Cards,OMIM and Pharm Gkv databases,and the intersection of VD and Pharmgk V was selected.The intersection database was uploaded to STRING to calculate the number of protein interactions,as well as Cytoscape3.9.1software,so as to obtain the topological network diagram of TCM--active ingredient--disease--target.GO function and KEGG path enrichment analysis and visualization processing were carried out in the intersection database.Results:1.Meta analysis: 20 randomized controlled trial literatures were included,including a total of 1714 patients,who were divided into observation group of Jiedu Tongluo Traditional Chinese medicine combined with Western medicine or basic treatment of VD and control group of Western medicine alone.Compared with the control group,the observation group improved(1)clinical efficacy(RR=1.26,95%CI=(1.19,1.32),P<0.00001)(2)MMSE score(MD=2.82,95%CI=(2.23,3.41),P<0.00001)(3)MOCA score(MD=4.15,95%CI=(3.49,4.81),P<0.00001)(4)HDS score(MD=3.41,95%CI=(1.78,5.03),P<0.00001)was better than that of the control group,and(1)TCM syndrome score(MD=-3.29,95%CI=(-3.67,-2.90)was reduced.P<0.00001)(2)homocysteine(HCY)value(MD=-3.66,95%CI=(-4.95,-2.38),P<0.00001)(3)inflammatory cytokines IL-6 value(MD=-7.15,95%CI=(-7.61,-6.68),(4)The inflammatory factor hs-CRP(MD=-1.91,95%CI=(-2.83,-0.99),P<0.00001)was better than the control group.ADL score(MD=4.27,95%CI=(-0.66,9.20),P=0.09)showed no statistically significant difference between the two groups.Subgroup analysis excluded the correlation between heterogeneity and intervention course,and considered that heterogeneity may come from methodological heterogeneity.the total incidence of adverse reactions in the observation group(5.51%)was lower than that in the control group(8.15%).2.Data mining: There were a total of 20 TCM prescriptions,with a total frequency of 218 times,involving 64 TCM,among which Stonecorus calamus,astragalus membranaceus,ligusticum Chuanxiong,salviorrhiza radix,Radix rehmanniae radix,angelica radix and Radix polygonatum were commonly used high-frequency drugs,involving a total of 14 TCM categories.The first four commonly used drugs were deficiency tonic drugs,blood-activating drugs for removing blood stasis,drugs for opening the body,drugs for resolving phlegm and relieving cough and asthma.A total of 35 association rules were obtained.Commonly used drug combinations were the second-order association rules of Radix acorus combined with astragalus,Radix Acorus combined with Chuanxiong,Radix Acorus combined with Salviae radix and Radix Rehmanniae radix,and the third-order association rules of Radix Rehmanniae combined with Radix Acorus + polygonatum,Radix acorus combined with Radix salviae radix.3.Network Pharmacology:A total of 25 active ingredients of calamus calamus,Astragalus membranaceus,Ligusticum Chuanxiong and radix rehmanniae radix were obtained,among which 16 were radix astragalus,6were ligusticus membranaceus,4 were calamus calamus and 2 were radix Rehmanniae radix(some traditional Chinese medicines contain the same ingredients),which acted on 150 targets of vascular dementia.The main active ingredients included quercetin,kawanferol,7-o-methyl isomysaccharides,etc.The core genes were JUN,MAPK1,TP53,AKT1,RELE,etc.GO function was enriched to 2273 biological processes(BP),including drug response,cell stress response,lipopolysaccharide reaction,etc.87 cells were composed of CC,including membrane raft,lipid raft,membrane region,etc.200 molecular functions(MFS),including nuclear receptor activity,ligand-activated transcription factor activity,NDN transcription factor binding sites,etc.KEGG was enriched to 174 pathways,including lipid and atherosclerosis,fluid shear stress and AGE-RAGE signaling pathways in atherosclerosis,diabetes complications,etc.Conclusions:1.The combination of Jiedu Tonglou Traditional Chinese medicine and Western medicine in the treatment of VD has certain advantages in improving the cognitive function,neurological function,improving the ability of daily living,clinical efficacy,reducing the HCY value,inhibiting inflammatory factors and other aspects,with high safety and low incidence of adverse reactions.It is an effective program for the treatment of VD,worthy of clinical promotion and application.2.Jidotongluo medicated calamus,Astragalus membranaceus,ligusticum Chuanxiong and Rehmanniae radix Rehmanniae played a core role in the treatment of VD.The common prescription laws were mainly deficiency supplementing drugs,with activating blood circulation to remove blood stasis and opening the body.The common drug combinations were calamus calamus with Astragalus membranaceus,ligusticus membranaceus,Radix Rehmanniae radix Rehmanniae,salviae miltiorrhiza,Radix Rehmanniae radix,etc.It has a certain guiding significance for clinical prescription medication.3.Detoxifying and collateralizing traditional Chinese medicine may improve learning and memory function,regulate lipid metabolism,inhibit inflammation and oxidation,protect vascular endothelial cells,repair damaged neurons and so on through multi-component,multi-point and multi-pathway synergistic relationship to achieve the purpose of VD treatment,providing certain reference for clinical treatment of VD,and providing direction for new drug research and development.