• Qi Lv, Manman Long, Xin Wang, Jie Shi, Pengtao Wang, Xiaoqin Guo, Jie Song, Adam C Midgley, Haojun Fan, and Shike Hou.
• Institute of Disaster and Emergency Medicine, Tianjin University, Tianjin, China.
• Shock. 2021 Dec 1; 56 (6): 102810391028-1039.

BackgroundCrush syndrome (CS) is the most common cause of deaths following earthquakes and other disasters. The pathogenesis of CS has yet to be fully elucidated. Thus, clinical choice of ideal drug treatments for CS remains deficient.Methods And ResultsIn this study, we first evaluated the relation between extrusion force and the severities of CS. Rats were exposed to different extrusion forces: 1 kg, 3 kg, 5 kg, and 8 kg, respectively. Survival rates, crushed muscle tissue edema, serum biochemical parameters, and histopathological staining were used to assess severity. Our results showed that there were no statistical differences in survival rate or changes in thigh circumference among the different extrusion forces groups. However, serum levels of potassium, creatine kinase, blood urea nitrogen, creatinine, and myoglobin were elevated at 12- and 24-h post-decompression in 5 kg and 8 kg groups, compared with 1 kg and 3 kg groups. Histopathological staining demonstrated that the degree of organ damage to kidney, muscle, and lung tissues correlated with increasing extrusion force. We next analyzed changes in serum protein profiles in 3 kg or 5 kg extrusion pressure groups. A total of 76 proteins (20 upregulated, 56 downregulated) were found to be altered at all three time points (0, 12, and 72 h) post-decompression, compared with the control group. Three common upregulated proteins alpha-1-acid glycoprotein (α1-AGP), neutrophil gelatinase-associated lipocalin (NGAL), and Haptoglobin were selected for validation of increased expression. α1-AGP was explored as a treatment for CS-induced acute kidney injury (AKI). Intraperitoneal injection of α1-AGP protected kidneys from CS-induced AKI by regulating TNF-α and IL-6 production, attenuating neutrophil recruitment, and reducing renal cell apoptosis.ConclusionOur findings demonstrated that the severity of crush injury is causally related to extrusion pressure and increase in blood serum markers. Our identification of the biomarker and treatment candidate, α1-AGP, suggests its implication in predicting the severity of CS and its use as a mediator of CS-induced AKI, respectively.Copyright © 2021 by the Shock Society.

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