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European Journal of Trauma and Emergency Surgery

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Open Access 28-02-2022 | Acute Kidney Injury | Original Article

Remote ischemic postconditioning protects against crush-induced acute kidney injury via down-regulation of apoptosis and senescence

Authors: Heng Jin, Xiaoxi Lin, Ziquan Liu, Jinqiang Wang, Jinxiang Wang, Yan Zhang, Chao Cao, Yanfen Chai, Songtao Shou

Published in: European Journal of Trauma and Emergency Surgery | Issue 6/2022

Abstract

Background

Acute renal failure due to crush syndrome is one of the leading causes of death in disasters. Ischemic Postconditioning (IPC) is a potentially effective strategy to protect against ischemic reperfusion injury, but a few studies noted its protective effect in crush induced acute kidney injury (AKI). Hence, this study investigated the optimal IPC strategy to prevent crush induced AKI and reveal related cellular mechanisms.

Methods

The right lower extremities of rabbits were constantly compressed for 8 h and then performed five cycles of clamping and releasing the femoral artery and vein before depression using a clip. In terms of the duration of clamping and releasing, the animals were randomly divided into 5 groups, Control, IPC-5sec, IPC-30sec, IPC-1min, and IPC-5min groups; 6 rabbits for each group. Biomarkers of inflammation, renal function, renal tubular injury, and muscular injury, apoptosis, and cellular senescence in kidney were detected.

Results

Six hours after decompression, the levels of Serum Creatine (SCr), Blood Urea Nitrogen (BUN), K+, and Interleukin-6 (IL-6) in IPC-1min and IPC-5min groups were lower than Control, with a statistically significant difference. The morphological study of Periodic Acid-Schiff (PAS) staining demonstrated that 6 h after decompression, IPC-1min can attenuate renal tubular damage renal tubule. Meanwhile, the level of Neutrophil Gelatinase-Associated Lipocalin (NGAL) in circulation in the IPC-30sec, IPC-1min, and IPC-5min groups was significantly decreased compared with the Control group, 2 h after decompression. On the other hand, the levels of serum Creatine Kinase (CK) and Myoglobin (Mb), and the morphological change of muscular damage detected by hematoxylin and eosin (H&E) staining in IPC-1min-treated group were significantly lower than Control group 6 hours after decompression. Further results of the cellular mechanism showed that the apoptotic markers of Terminal deoxynucleotidyl Transferase-mediated dUTP Nick End Labeling (TUNEL) and Caspase3 and the cell senescent markers of senescence-associated β-galactosidase (SA-β-Gal) and nuclear LAMNB1 have changed significantly in the IPC-1min group, compared with the control group.

Conclusions

Performing 5 cycles of 1-min IPC would be a convenient, time-saving, and effective method to prevent crush-induced AKI by attenuating the release of nephrotoxic substances after decompression and downregulation of the expression of apoptosis and cellular senescence biomarkers.

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Title: Remote ischemic postconditioning protects against crush-induced acute kidney injury via down-regulation of apoptosis and senescence
Authors: Heng Jin
Xiaoxi Lin
Ziquan Liu
Jinqiang Wang
Jinxiang Wang
Yan Zhang
Chao Cao
Yanfen Chai
Songtao Shou
Publication date: 28-02-2022
Publisher: Springer Berlin Heidelberg
Keywords: Acute Kidney Injury
Acute Kidney Injury
Published in: European Journal of Trauma and Emergency Surgery / Issue 6/2022
Print ISSN: 1863-9933
Electronic ISSN: 1863-9941
DOI: https://doi.org/10.1007/s00068-022-01910-5

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Remote ischemic postconditioning protects against crush-induced acute kidney injury via down-regulation of apoptosis and senescence

Abstract

Background

Methods

Results

Conclusions

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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