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Method: Forty male SD rats were randomly dived into four groups, control (saline), low dose (10mg/kg xylazine), median dose (20mg/kg xylazine) and high dose (40mg/kg xylazine). And the rats were injected the drug intraperitoneal continuous 28 days, and then collected serum and liver tissues, Elisa, RNA sequencing, histopathology examination, RT-qPCR were performed. Results: Compared to the control group, the body weight of 40mg/kg group was decreased, the level of ALT and AST in serum of 40mg/kg group was increased. Histopathological examination showed fatty degeneration, necrosis and fibrosis of the liver. 192 up-regulated and 277 down-regulated genes were identified through RNA sequencing in the 40mg/kg group and the PPAR signaling pathway ranked first in the KEGG pathway analysis, The common DEG in the 10mg/kg and 40mg/kg (Lox), four common DEGs in the 20mg/kg and 40mg/kg (Srebf1, Nr1dl, Fasn, SCD1), and four genes PCK1, FABP5, ACOX2, CPT2 in the PPAR signaling pathway in the 40mg/kg group were validated through Real-Time PCR Analysis. Conclusion：Long term xylazine injection can cause liver injury and the PAPR signaling pathway play a core role in the process of xylazine related liver injury. Overall design: Forty male SD rats were randomly dived into four groups, control (normal saline), low dose (10mg/kg xylazine), median dose (20mg/kg xylazine) and high dose (40mg/kg xylazine) and injected 28 days to investigate the liver injury of xylazine."],"repository":["ENA"],"additional_accession":[]},"is_claimable":false,"name":"mRNA-sequencing uncovered the underlying mechanisms of xylazine related liver injury","description":"mRNA-sequencing uncovered the underlying mechanisms of xylazine related liver injury","dates":{"last_updated":"2025-09-24","first_public":"2025-01-07"},"accession":"PRJNA1129485","cross_references":{"GEO":["GSE271044"],"taxon":["10116"],"PubMed":["39692361"]}}