Department of Joint Surgery, Honghui Hospital, Xi'an Jiaotong University, No. 555 Youyi East Road, Beilin District, Xi'an, Shaanxi Province, 710054, People's Republic of China.
J Orthop Surg Res. 2022 Jan 15;17(1):20. doi: 10.1186/s13018-021-02903-7.
The 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.
Seventy-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.
Nine 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.
The 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.
肺损伤通常继发于严重创伤。在挤压综合征模型中，可能存在继发的肺损伤。我们假设高迁移率族蛋白 B1（HMGB1）从肌肉组织中释放出来，通过 HMGB1/晚期糖基化终产物受体（RAGE）/c-Jun N 末端激酶（JNK）途径介导肺泡上皮细胞（AEC）的凋亡。本研究旨在探讨 HMGB1 如何介导大鼠模型中 AEC 的凋亡。
75 只 SD 雄性大鼠随机分为五组：CS 组、CS+载体组、CS+乙基丙酮酸（EP）组、CS+FPS-ZM1 组和 CS+SP600125 组。当大鼠 CS 模型完成 24 小时后，处死大鼠。我们收集血清和全肺组织。血清样本中炎症细胞因子的测量。Western blot 和 RT-qPCR 用于定量蛋白质和 mRNA。最后，通过 TUNEL 检测凋亡细胞。我们使用 SPSS 25.0 进行统计分析。
9 只大鼠在实验过程中死亡。死亡的大鼠被排除在进一步分析之外。与 CS 组相比，CS+EP、CS+FPS-ZM1 和 CS+SP600125 组血清中 HMGB1 和炎症细胞因子水平下调。Western blot 和 RT-qPCR 分析显示，CS+EP、CS+FPS-ZM1 和 CS+SP600125 组与 CS 组相比，HMGB1、RAGE 和磷酸化-JNK 显著下调，排除总-JNK mRNA。用 TUNEL 评估 AEC 的凋亡。我们发现 CS+EP、CS+FPS-ZM1 和 CS+SP600125 组 TUNEL 阳性细胞减少。
挤压伤后早期即出现远隔肺损伤。HMGB1/RAGE/JNK 信号轴是阻断挤压伤后 AEC 凋亡的一个有吸引力的靶点。
