Abstract
ObjectivesThe lung injury is often secondary to severe trauma. In the model of crush syndrome, there may be secondary lung injury. We hypothesize that high-mobility group box 1 (HMGB1), released from muscle tissue, mediates the apoptosis of alveolar epithelial cells (AEC) via HMGB1/Receptor of advanced glycation end-products (RAGE)/c-Jun N-terminal kinase (JNK) pathway. The study aimed to investigate how HMGB1 mediated the apoptosis of AEC in the rat model.MethodsSeventy-five SD male rats were randomly divided into five groups: CS, CS + vehicle, CS + Ethyl pyruvate (EP), CS + FPS-ZM1 group, and CS + SP600125 groups. When the rats CS model were completed after 24 h, the rats were sacrificed. We collected the serum and the whole lung tissues. Inflammatory cytokines were measured in serum samples. Western blot and RT-qPCR were used to quantify the protein and mRNA. Lastly, apoptotic cells were detected by TUNEL. We used SPSS 25.0 for statistical analyses.ResultsNine rats died during the experiments. Dead rats were excluded from further analysis. Compared to the CS group, levels of HMGB1 and inflammatory cytokines in serum were downregulated in CS + EP, CS + FPS-ZM1, and CS + SP600125 groups. Western blot and RT-qPCR analysis revealed a significant downregulation of HMGB1, RAGE, and phosphorylated-JNK in CS + EP, CS + FPS-ZM1, and CS + SP600125 groups, compared with the CS groups, excluding total-JNK mRNA. Apoptosis of AEC was used TUNEL to assess. We found the TUNEL-positive cells were downregulated in CS + EP, CS + FPS-ZM1, and CS + SP600125 groups.ConclusionThe remote lung injury begins early after crush injuries. The HMGB1/RAGE/JNK signaling axis is an attractive target to abrogate the apoptosis of AEC after crush injuries.
Highlights
Crush injuries are severe soft tissues damage in the field of orthopedic trauma
Western blot and RT-qPCR analysis revealed a significant downregulation of high-mobility group box 1 (HMGB1), Receptor of advanced glycation end-products (RAGE), and phosphorylated-Jun N-terminal kinase (JNK) in crush syndrome (CS) + Ethyl pyruvate (EP), CS + FPS-ZM1, and CS + SP600125 groups, compared with the CS groups, exclud‐ ing total-JNK mRNA
We found the transferase-mediated dUTP nick end-labeling (TUNEL)-positive cells were downregu‐ lated in CS + EP, CS + FPS-ZM1, and CS + SP600125 groups
Summary
Crush injuries are severe soft tissues damage in the field of orthopedic trauma. Prolonged compression of limb muscles and subsequent decompression is essential in the development of crush syndrome (CS) [1], includingZhang et al Journal of Orthopaedic Surgery and Research (2022) 17:20 hyperkalemia, metabolic acidosis, hypovolemic shock, acute kidney injury, and disseminated intravascular coagulation [2]. Crush injuries are severe soft tissues damage in the field of orthopedic trauma. The sequential damage in the kidney after crush injury is not the unique dysfunctional organ [3]. The lung injury has been observed clinically after severe trauma. This lung injury is secondary to the trauma, and likely due to an elevation in leukocytes and inflammatory cytokines in the lung tissue [10]. Duration of the treatment of trauma and the lung injury is often paid attention to when finding worse pulmonary function. It may be that the lung injury begins at the time of decompression. We should notice that the remote lung injury at the early stage
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
