Welcome to Chinese Journal of Clinical Pharmacology and Therapeutics,Today is Chinese

Chinese Journal of Clinical Pharmacology and Therapeutics ›› 2025, Vol. 30 ›› Issue (1): 11-19.doi: 10.12092/j.issn.1009-2501.2025.01.002

Previous Articles     Next Articles

Nrf1 attenuates neuronal injury caused by oxygen glucose deprivation/reperfusion via inhibiting apoptosis

XIA Rongsong1,2, YANG Jing2, WANG Hong1, PENG Zhe3, ZHAO Yibei1, YANG Junqing1   

  1. 1 Key Laboratory of Biochemistry and Molecular Pharmacology, Department of Pharmacology, Chongqing Medical University, Chongqing 400016, China; 2 Department of Pharmacy, Chongqing General Hospital, Chongqing 401147, China; 3 Department of Pharmacy, Women and Children's Hospital of Chongqing Medical University, Chongqing 401147, China
  • Received:2024-01-08 Revised:2024-04-22 Online:2025-01-26 Published:2025-01-02

Abstract:

AIM: To investigate the effects of Nrf1 on neuronal apoptosis treated by oxygen-glucose deprivation/reperfusion and the mechanism. METHODS: Single-cell sequencing data was analyzed by GEO database, and the correlation of Nrf1 expression with apoptotic pathways evaluated based on GSVA package calculations. PC12 cells and primary neurons were divided into the Normal group, the OGD/R group, the OGD/R+ siRNA-NC group, and the OGD/R+ Nrf1-siRNA-2 group. Cell images was observed by laser scanning confocal microscopy; the viability of cells were detected by MTT assay; the apoptosis of cells were detected by flow cytometry; DHE fluorescent probe to detect ROS levels, the protein expression of Nrf1,bcl-2 and Bax were detected by Western blot; and nuclear translocation was observed by laser scanning confocal microscope. RESULTS: The results of biosignature analysis revealed that Nrf1 was mainly enriched in the apoptotic pathway; compared with normal group, the cell body became smaller, synapse broke, cells clustered in PC12 cells and primary neurons with OGD/R treated, and the vitality of PC12 cells and neuronal were decreased significantly (P<0.01); ROS levels were significantly higher (P<0.01), the expressions of Nrf1 and Bax were increased significantly, and the expression of bcl-2 was decreased significantly (P<0.05). Compared with the OGD/R group, there was no significant difference in the siRNA-NC group; compared with the siRNA-NC group, the viability of cells was decreased significantly (P<0.01); ROS levels were significantly increased (P<0.01), the expressions of Nrf1 and Bax were increased markedly, and the expressions of bcl-2 was decreased significantly (P<0.05) in Nrf1-siRNA-2 group. CONCLUSION: Nrf1 attenuates neuronal injury caused by oxygen glucose deprivation/reperfusion via inhibiting apoptosis.

Key words: OGD/R, Nrf1, Bax, bcl-2, apoptosis

CLC Number: