安徽医科大学学报2025，Vol.60Issue(11)：2052-2058,7.DOI:10.19405/j.cnki.issn1000-1492.2025.11.009
高原低氧通过NOD样受体信号通路诱导小鼠肾脏细胞焦亡
Plateau hypoxia induces pyroptosis in mouse kidney cells through NOD-like receptor signaling pathway
摘要
Abstract
Objective 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,CASP 11,GSDMD,IF I1 6,NAIP5,IRF9,and the downstream inflammatory factors,IL-1 β 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.关键词
低氧/肾脏/转录组学/NOD样受体信号通路/炎症因子:细胞焦亡Key words
hypoxia/kidney/transcriptomics/NOD-like receptor signaling pathway/inflammatory factor/pyrop-tosis分类
医药卫生引用本文复制引用
许鑫桐,陈晓晨,崔成玲,王昕,高翔..高原低氧通过NOD样受体信号通路诱导小鼠肾脏细胞焦亡[J].安徽医科大学学报,2025,60(11):2052-2058,7.基金项目
国家自然科学基金(编号:82060295) （编号:82060295）
青海省科技计划(编号:2023-ZJ-771) National Natural Science Foundation of China(No.82060295) （编号:2023-ZJ-771）
Science and Technology Pro-ject of Qinghai Province(No.2023-ZJ-771) （No.2023-ZJ-771）
