Department of Critical Care Medicine, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, No. 17 Yongwaizheng Street, Nanchang, Jiangxi, 330006, China.
Department of Emergency, The Affiliated Ganzhou Hospital of Nanchang University, Ganzhou, Jiangxi, China.
Funct Integr Genomics. 2024 Oct 25;24(6):200. doi: 10.1007/s10142-024-01469-x.
Septic lung injury is an unmet clinical challenge due to its high mortality, and there is a lack of effective treatment. Accumulating evidence suggests that an uncontrolled pulmonary inflammatory response is important in the pathogenesis of lung injury in sepsis. Therefore, limiting excessive early inflammatory responses may be an effective strategy. We established a septic lung injury model using cecal ligation and puncture. Western blotting and immunofluorescence analyses were performed to assess the expression of PTP1B and endoplasmic reticulum (ER) stress and pyroptosis. Co-immunoprecipitation was used to analyze the binding of PTP1B and Src molecules. PTP1B is upregulated in both in vivo and in vitro models of septic lung injury. PTP1B directly binds to Src and aggravates inflammation by regulating the ER stress-pyroptosis axis. The inhibition of PTP1B alleviates inflammation and improves the prognosis of septic mice. Our study suggesting that PT1B inhibitors have clinical application value in the treatment of septic lung injury. This may provide a new strategy for the treatment of septic lung injury.
脓毒症性肺损伤是一种未满足的临床挑战，因为其死亡率高，且缺乏有效的治疗方法。越来越多的证据表明，失控的肺部炎症反应在脓毒症性肺损伤的发病机制中很重要。因此，限制早期过度炎症反应可能是一种有效的策略。我们使用盲肠结扎和穿刺术建立了脓毒症性肺损伤模型。通过 Western blot 和免疫荧光分析来评估 PTP1B 和内质网（ER）应激及细胞焦亡的表达。通过共免疫沉淀分析 PTP1B 和Src 分子的结合。在脓毒症性肺损伤的体内和体外模型中，PTP1B 均上调。PTP1B 通过调节 ER 应激-细胞焦亡轴直接与 Src 结合，加重炎症。PTP1B 的抑制减轻了炎症并改善了脓毒症小鼠的预后。我们的研究表明，PTP1B 抑制剂在治疗脓毒症性肺损伤方面具有临床应用价值。这可能为脓毒症性肺损伤的治疗提供新策略。
