Abstract: Objective To analyze changes of serum metabolites in two-kidney-one-clip (2K1C) renal hypertension rats and sham-operated rats based on the gas chromatography-time-of-flight mass spectrometry (GC-TOF/MS) technology. Methods Twenty healthy male SD rats were randomly divided into sham operation group and 2K1C model group with 10 rats in each group. The changes of body mass and tail artery systolic pressure before modeling and four weeks after modeling were compared between the two groups of rats. GC-TOF/MS was used to detect the expression level of serum metabolites, and orthogonal partial least squares discriminant analysis (OPLS-DA) was used to screen out the differential metabolites. The screened differential metabolites were analyzed by Cluster analysis and KEGG pathway analysis. Results A total of 7 rats were successfully modeled after 4 weeks in the 2K1C model group. Compared with the Sham group, a total of 14 differentially expressed metabolites were screened in the 2K1C model group, including up-regulated arachidonic acid, hippuric acid, heptadecanoic acid, indolelactate, xylose, cis-gondoic acid, fumaric acid, cytidine-monophosphate, lactamide, 2-hydroxy-3-isopropylbutanedioic acid and biuret, and down-regulated tyrosine, cholic acid and stigmasterol. These differential metabolites were closely related to energy metabolism, amino acid metabolism, lipid metabolism and primary bile acid biosynthesis. Conclusion The changes of serum metabolites in 2K1C hypertensive rats are involved in various pathways such as energy metabolism, which in turn affects the pathophysiological process of renal hypertension.

Key words: hypertension, renal, metabolomics, gas chromatography-mass spectrometry, cluster analysis, rats, Sprague-Dawley, two-kidney-one-clip