Aim Renal interstitial fibrosis （RIF） is a common final pathological process in the progression of kid- hey disease. To investigate the pathogenesis of RIF and offer invaluable instructions for diagnosis and therapy treat- 1 ment of RIF. Method： H NMR based-metabolomics study on targeted kidney tissue of RIF rats induced by uni- lateral ureteral obstruction was conducted combined with multivariate data analysis to characterize the alteration of endogenous metabolites and elucidate the molecular mechanism of RIF. Results The combination of a variety of statistical methods was used to screen out 14 potential significantly changed metabolites, including increased levels of lactate, methionine, aspartate, allantoin, uracil, 3-HB and decreased levels of TMAO, leucine, valine, lysine, adenosine, adenine, tyrosine and phenylalanine in the left kidney of UUO rats, compared with SO rats. To gain ad- ditional insight about the relationship between metabolites, they were mapped to KEGG IDs and built compound network by Metscape reflecting the complex pathology and providing evidence for the involvement of such processes as altered amino acid metabolism, adenine metabolism, energy metabolism, osmolyte change and induced oxidative stress. In addition, we have explored the morphology and size, calculated the degree of fibrosis based on altered differential metabolites, and speculated the probable causes of moderate RIF of contralateral kidneys to help to un- derstand the disease, which was also supported by serum biochemistry and kidney histopathology results. In addi- tion, the correlation analysis of the pathological parameters （ clinical chemistry, histological and immunohistochem- istry results） with the significantly changed differential metabolites responsible for the cluster （different groups） was also performed. Conclusion Our work shows that target tissue metabolomics analysis can be used as a power-ful tool to gain a better understanding of the mechanism of the disease and provide a novel insight in the pathogene- sis of RIF.
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