〔Abstract〕 To investigate the molecular mechanism of NOD-like receptor (NLR) signaling pathway in- duced cellular focal death in mouse kidney tissues under plateau hypoxia based on transcriptomic sequencing tech- nology . Methods Animal models were constructed in high-altitude kidney test group (HKT group) and plain kid- ney control group (PKC group) , and C57/BL6 mice were bred at an altitude of 4 200 m and 400 m , respectively . Kidney tissues were aseptically taken out after 30 d and used for observation of renal histopathological changes and transcriptomics sequencing , respectively , and then differentially expressed genes (DEGs) were enriched by KEGG and GO analysis . Key gene and protein expression levels were verified by reverse transcription quantitative polymer- ase chain reaction (RT-qPCR) and Western blot analysis . Results Hematoxylin-eosin (HE) staining showed that the renal tubules of HKT mice were disorganized , and the tubular epithelial cells were edematous with inflammatory cell aggregation . Transcriptomics sequencing analysis revealed that a total of 3 007 DEGs were identified in the HKT group , and KEGG analysis showed that DEGs were significantly enriched in the NLR signaling pathway . The mRNA expression of the key differentially expressed genes , CASP1 , CASP11 , GSDMD , IFI16 , NAIP5 , IRF9 , and the downstream inflammatory factors , IL-1β and IL-18 , was upregulated , and protein expression of CASP1 , CASP11 , and GSDMD was up-regulated . Conclusion The plateau hypoxic environment induces cellular pyropto- sis by regulating the expression of NLR signaling pathway and releases downstream inflammatory factors to cause in- flammatory responses .