In this study,transcriptomics analysis of aristolochic acid I (AAI) induced acute kidney injury was carried out to explore the molecular mechanism of AAI nephrotoxicity.Fifteen male C57BL/6 mice were randomly divided into normal group (n=6) and model group (n=9).The mice in the model group were intraperitoneally injected with 20 mg/kg AAI once a day for consecutive 5 days and sacrificed on the 6th day.Serum and renal tissue were collected for later detection,Scr and BUN values were detected,and HE staining of renal tissue was performed to observe pathological changes.High-throughput transcriptome sequencing was performed on RNA extracted from kidney tissue samples,which randomly selected from each group.Fold change ≥ 2.0 as well as P-value < 0.01 were defined as differentially expressed genes,which screened separately. Meanwhile, functional analysis was performed using GO and KEGG databases.The top 5 genes with the most obvious difference multiple changes between the two groups were selected for qRT-PCR verification.Compared with the normal group,Scr and BUN of the model group were significantly increased,HE staining showed that the kidney tissue in normal group had a normal structure,and the glomeruli,tubules,interstitium were not obviously changed.While in model group,the kidney tissue turned out globular edema,glomerular pyknosis,and loss of proximal convoluted tubule epithelial cells.Through high-throughput transcriptome sequencing,a total of 4 975 differential mRNAs were obtained,of which 2 511 were up-regulated genes and 2 464 were down-regulated genes.Cluster analysis identified Kap,Spp1,Aldh1a2,Serpine1,Tnc as the top 5 differentially expressed genes.GO and KEGG enrichment analysis found that these differential genes were mainly significantly enriched in GO categories related to small molecule metabolism,extracellular matrix tissue,immune response involving neutrophils,granular cavity and cytoplasmic vesicle cavity.It is also significantly enriched in pathways such as inflammatory signaling,peroxidation,and glucose metabolism.qRT-PCR indicated that the expression of Kap decreased,while the expression of Spp1,Aldh1a2,Serpine1 and Tnc increased in model group,which were consistent with the transcriptome results.The results suggest that AAI has obvious nephrotoxicity,and its toxic mechanism may be related to inflammatory response,oxidative stress,glucose metabolism and other pathways.