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Abstract: TH-PO038

Impact of Mechanical Ventilation Time on Ferroptosis in Renal Ischemia-Reperfusion Injury in Rats

Session Information

Category: Acute Kidney Injury

  • 103 AKI: Mechanisms

Authors

  • Zhou, Fangfang, HwaMei Hospital, University of Chinese Academy of Sciences, Ningbo City, Zhejiang, China
  • Yang, Yi, Zhejiang University, Hangzhou, China
  • Luo, Lianxin, HwaMei Hospital, University of Chinese Academy of Sciences, Ningbo City, Zhejiang, China
  • Luo, Qun, HwaMei Hospital, University of Chinese Academy of Sciences, Ningbo City, Zhejiang, China
Background

Prolonged mechanical ventilation was considered as a risk factor for acute kidney injury(AKI) in previous studies, while the underlying mechanisms remain unclear. Ferroptosis is a recently discovered form of programmed cell death that is characterized by iron-dependent accumulation of reactive oxygen species. The present study aimed to investigate the impact of mechanical ventilation (MV) time on ferroptosis in renal ischemia/reperfusion injury (IRI) in rats.

Methods

32 Male-adult SD rats were divided into 4 groups: Group 1 (Sham operation) ; Group 2 (IRI: subjected to 45-min bilateral renal ischemia); Group 3 (IRI and underwent MV 4hours ); Group 4 (IRI and underwent prolonged MV (12hours)) . At 12hours after IRI, animals were euthanized. Kidney function was evaluated by Scr. Morphological changes associated with kidney injury and ferroptosis were assessed by HE staining and electron microscopy. Central regulator of ferroptosis GPX4, GSH, the lipid peroxidation markers 4HNE and SOD2 were measured in kidney tissue by Western blot analysis. The level of inflammatory cytokine (TNF-α) was assessed in plasma by ELISA.

Results

Scr was significantly higher in Group 4 than in Groups 1, 2 (P<0.01). Scr also increased in Group 3 than Groups 1,2, but with no statistical significance (P >0.05). By HE staining, Group 4 showed the most severe morphological kidney damage, characterized by increased interstitial edema and tubular dilatation than Group 1,2,3.Plasma TNF-α increased with the prolonged MV time, and Group 4 showed the highest level , achieving statistical significance when compared to Group 1 (P<0.05). In kidney tissue, protein expressions of GPX4,GSH and SOD2 progressively decreased from Groups 1 to 4, and Group 4 showed the lowest level, achieving statistical significance(GPX4 and GSH, P<0.05; SOD2, P<0.01). Protein expressions of 4HNE progressively increased from groups 1 to 4, and Group 4 showed the highest level, achieving statistical significance(P<0.05). Electron microscopy also revealed abnormal mitochondrial morphology of ferroptosis in Group 4, which is characterized by the presence of smaller mitochondria and reuced/absent cristae.

Conclusion

Our present data showing that prolonged MV time may worsen kidney injury by ferroptosis, which is linked to the GPX4-GSH system, following lipid peroxidation. It may be mediated by stimulated inflammation.

Funding

  • Government Support - Non-U.S.