Effects And Mechanisms Of Polycyclic Aromatic Hydrocarbons In PM2.5 On The Treatment Of Membranous Nephropathy With Warming Yang And Relieving Exterior Symptom

PurposeTo explore the pathways of PM2.5 organic pollutant components acting on idiopathic membranous nephropathy,and to summarize the intervention mechanism of"Wenyangjiebiao" method in the treatment of idiopathic membranous nephropathy.MethodPart I:Clinical efficacy of Wenyangjiebiao method in the treatment of idiopathic membranous nephropathy and the relationship between polycyclic aromatic hydrocarbon DNA adducts and different stages of the disease① This study is a prospective cohort study.Between June 2020 and September 2022,we collected blood and urine specimens from 45 patients with idiopathic membranous nephropathy and 43 healthy individuals before and after treatment to test the efficacy index.② ELISA method was used to test serum levels of PAH metabolites(PAH DNA adducts).③We performed the analysis of different subgroups and relationship with clinical indicators.Part II:mRNAs co-altered by PM2.5 and MN and target genes of differentially expressed miRNAs in MNWe used bioinformatics analysis to find possible targets for the action of PAHs and their components on MN patients.We downloaded four datasets from the NCBI Gene Expression Omnibus database,including two mRNA expression profile datasets and two microRNA expression profile datasets.The GEO2R tool was used to select DEGs and DE microRNAs.DEGs were heat mapped using BIC.We performed visualisation and comprehensive analysis of enriched pathways through the Metascape online database.PPI networks was performed using Cytoscape as well as CytoHubba plug-in.In addition,the online database TargetScan was used to identify the target genes of differentially expressed microRNAs.ResultPart Ⅰ:Clinical efficacy of Wenyangjiebiao method in the treatment of idiopathic membranous nephropathy and the relationship between polycyclic aromatic hydrocarbon DNA adducts and different stages of the disease①In clinical studies,Chinese herbal treatment options have significant clinical efficacy.The 24-hour urine protein quantification was significantly lower and serum albumin was significantly higher(P<0.05).The remission rate for the 45 patients was 60%,with a total of 27 patients entering remission.② PAHDNA is consistently higher in the active group of patients.It has potential predictive value for prognostic staging of disease(AUC=0.819,P<0.05,95%CI 0.672-0.965).③ PAHDNA correlated linearly with 24-hour urine protein quantification,albumin and lipids in 45 patients with IMN.Part Ⅱ:mRNAs co-altered by PM2.5 and MN and target genes of differentially expressed miRNAs in MNUsing comprehensive bioinformatics analysis,After B[a]P treatment,DEGs centered on TMEM167A,including CABLES1,OLIG3,ASB2,TIPARP,CYP1B1,CYP1A1.DEGs in IMN include HLA-DQA,RPS,TMEM167A.For the analysis of non-coding RNA datasets,differentially expressed microRNAs co-target TMEM167A,among others,and are functionally enriched for T/B cell immunity,autophagic pathways,etc.Key genes may act mainly through stress,immune and autophagic pathways when organic pollutant components intervene or in MN disease states.Conclusion1.The "Wenyangjiebiao" method,which is based on Mahuang Fuzi Decoction and Shenzhuo Decoction,is effective in relieving idiopathic membranous nephropathy with the advantage of low recurrence rate and high safety.The increased concentration of metabolites of organic pollutants PAHs in the human body may be related to the active disease state of patients with idiopathic membranous nephropathy.This process may be achieved through stimulation of inflammatory pathways.2.Bioinformatics analysis revealed that PAHs,represented by benzo[a]pyrene,may be involved in idiopathic membranous nephropathy through stress,immune inflammation,and autophagy pathways.