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MicroRNAs-biomarker Screening And Mechanism Study Of MicroRNAs For Diabetic Nephropthy Treated With Tangshen Formula

Posted on:2019-08-05Degree:MasterType:Thesis
Country:ChinaCandidate:C L HuangFull Text:PDF
GTID:2404330569999247Subject:Chinese materia medica
Abstract/Summary:PDF Full Text Request
Diabetic Nephropathy(DN)is one of the major microvascular comlications caused by type 1 and 2 diabetes and is also a major cause of global end-stage renal disease.The main clinical manifestations are large number proteinuria,anemia appearance,renalinsufficiency,and elevated blood pressure or edema.In recent years,the rate of disease is gradually increasing.According to statistics,The number of patients suffering from diabetes worldwide will reach 3 billion by 2025.DN has become a major disease that threatens human health.At present,The research mechanism of DN is unclear.The diagnosis of DN is mainly focused on biochemical indicators such as urinary protein and serum creatinine at domestic and foreign.At present,it has not been found a effective and diagnostic plasma markers in DN.t has not yet been able to find a very effective diagnosis of DN.A very effective,diagnostic plasma marker.Objective: To compare the expression of miRNAs in clinical patients among different groups,including before and after administration of Tangshen Formula,to screening of miRNA markers for diabetic nephropathy with Tangshen Formula,and discussion on the mechanism of pharmacodynamics ofTangshen Formula from the perspective of regulation of circulating miRNA expression.This study lays a foundation for the study on the effectiveness of Tangshen Formula in the treatment of diabetic nephropathy.Methods: DN patients were randomly divided into two groups: placebo treatment group and Tangshen Formula treatment group.Plasma samples before,2 months,4 months and 6 months before and after treatment were collected from two groups of patients respectively.The serum from before and after 6 months of treatmen were checked with microRNA microarray assay andones.Through the analysis of expression profiles of miRNAs between groups and before and after treatment,combined with bioinformatics analysis,Screening potential miRNAs markers associated with the efficacy of glycosides.Thereafter,the potential miRNA markers were further quantified using digital PCR.Quantitative detection of miRNAs in plasma samples before and 2 months,4 months and 6 months of treatment was performed to explore the treatment of glycosides and kidneys.Expression Pattern and Mechanism of miRNAs Markers in the Process.Conclusion: Comparative analysis of plasma circulatory miRNAs expression profiles revealed significant differences in plasma miRNAs expression between the Tangshen Formula treated group and the placebo treated group,and 158 differentially expressed miRNAs were screened.Through the bioinformatics analysis of differentially expressed genes,it wasfound that Tangshen Formula mainly regulates Toll like signaling pathway,Cytokine-cytokine receptor interaction,TGF-beta signaling pathway,Jak-STAT signaling pathway,PPAR signaling pathway,and Cell adhesion molecules(Signaling pathways such as CAMs,Hematopoietic cell lineage,and adipocytokines play a role.Quantitative determination of six core-regulated differentially expressed miRNAs was screened and confirmed as a potential miRNA marker for diabetic nephropathy.Significance: Through in-depth study on the expression of plasma circulating miRNAs,this article initially explained the mechanism of the whole signal pathway regulation of diabetic nephropathy treated by Tangshen Formula,and discovered six potential miRNAs markers,which were quantitatively verified.It can provide a reference basis for the evaluation of the efficacy of traditional Chinese medicine compound Tangshen Formula,and lay a foundation for the in-depth study of the efficacy of Tangshen Formula in the treatment of diabetic nephropathy.
Keywords/Search Tags:Tangshen formula, Diabetic Nephropathy, Biomarkers, miRNA expression microarray, Digital PCR
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