Urine Metabonomic Research Of The Effect Of Shendibushen Capsule On Renal Fibrosis Rat

Objective:Through biochemical,histopathological and his topathological studies,it is clear that unilateral ureteral obstruetion(UUO)can induce renal fibrosis in rats.On this basis,urinary metabolomics associated with histological progress ion were utilized to explore the pathogenesis of renal fibrosis(RF),and screening potential biomarkers to illustrate the metabolic cycle way and signal transduction pathways in R F.Based on the above research,the therapeutic effect and mechanism of shendibushen capsule on RF were clarified from three aspects about serum biochemistry,pathology and metabolomics.Methods:1.RF rat model was established by unilateral uret eral obstruction.Then,analysising the pathophysiological changes of rats by comparing the general state,weight,24-hour urine,urine micro albumin,urea nitrogen,creatinine and histopathological between the blank group and model group rats.Urine of RF model group collected in every week were used for metabonomic analysis by UPLC-QTOF-MS.Differential metabolites of RF were identified by data acquired from metabolomics combined with related information of HMDB,MassBank and PUB MED.Then,the key biomarkers were selected by hierarchical clustering analysis,MetPA(Metabolomics Pathway Analysis)and the receiver-operating characteristi c(ROC)analysis.Finally,analysising the changes of key biomarkers in progressive RF were analysised and their biological significances were clarified.2.A certain concentration of shendibushen capsule solution were administered to rats with renal fibrosis that were induced by UUO.The therapeutic effect of shendibushen capsule on renal fibrosis rats was observe d by detecting 24-hour urine,urine microalbumin,urea nitrogen,creatinine and histopathological changes in kidney.3.Urine of RF model rats were used for metabono mic analysis by UPLC-QTOF-MS,the data were identified by principal component analysis and partial least-sqwares-discriminant analysis.Then,urinary metabolic profiling was performed to clarify their mechanisms of anti-fibrosis by analyzing impact of the drug on content of potential biomarkersResults:1.The model of renal fibrosis was established by unilateral ureteral obstruction of rats.61 differential metabolites in urine of RF rat were identified,they are 27 positive ions and 34 negative ions.From these,we selected 12 metabolites as the key pot ential biomar ker,which involving one carbon pool by folate,amino sugar and nucleotide sugar,fructose and mannose,gly oxylate and dicarboxylate,vitamin B6,histidine,β-A1a nine,propanoate metabolism and alanine,aspartate,glutamate metabolism.These may be the most relevant metabolic pathways about RF.2.Shendibushen capsule could increase 24h total volume of urine,reduce protein content in urine,lower the level of creatinine and urea nitrogen in serum and all eviate the process of renal lesions.3.Shendibushen capsule could participate in regulating histidine metabolism and Propanoate metabolism to reduce inflammation and oxidative stress,regulating as partic acid metabolism to improve glomerular filtration function and regulating vitamin B 6 metabolism improves renal anemia and malnutrition.Conclusions:12 potential biomarkers in the progression of renal fibrosis,Shendibushen capsule could reduce inflammation and oxidative stress,improve the function of glomerular filtration,improve renal anemia and malnutrition,and thus play the role of anti-fibrosis by regulating 6 key potential biomarkers of them.