Zhang Xinxin, Wang Xingsheng, Sun Li, Gao Guangsheng, Li Yun
Department of Emergency Medicine, Fuyang People's Hospital of Anhui Medical University, Fuyang, Anhui, China.
Intensive Care Unit, Central Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China.
J Inflamm (Lond). 2023 Feb 3;20(1):5. doi: 10.1186/s12950-023-00332-3.
Acute lung injury is a major cause of death in sepsis. Tofacitinib (TOFA), a JAK inhibitor, has anti-inflammatory activity in autoimmune diseases, but its role in acute lung injury in sepsis remains unclear. The purpose of this study is to establish a septic rat model by cecal ligation and perforation, and to evaluate the effect of tofacitinib on the survival rate of septic rat model and its role in acute lung injury in septic rats and the possible mechanism of action. In this study, TOFA (1 mg/kg, 3 mg/kg, 10 mg/kg) was used to observe the survival rate of septic rats. It was found that TOFA (10 mg/kg) significantly improved the survival rate of septic rats. We selected TOFA (10 mg/kg) and focused on the protective effect of TOFA on acute lung injury. The results confirmed that TOFA significantly inhibited the expression of TNF-α, IL-1β, IL-6 and IFN-γ inflammatory factors, reduced the W/D weight ratio of septic lung tissue, and significantly improved lung histopathological damage. These results may be related to the inhibitory effect of TOFA on JAK-STAT/NF-κ B signaling pathway. In conclusion, for the first time, we found that TOFA has a protective effect against sepsis-induced acute lung injury, and it may be a promising drug for the treatment of acute lung injury in sepsis.
急性肺损伤是脓毒症患者死亡的主要原因。托法替布（TOFA）是一种JAK抑制剂，在自身免疫性疾病中具有抗炎活性，但其在脓毒症急性肺损伤中的作用尚不清楚。本研究旨在通过盲肠结扎穿孔建立脓毒症大鼠模型，评估托法替布对脓毒症大鼠模型存活率的影响及其在脓毒症大鼠急性肺损伤中的作用和可能的作用机制。本研究中，使用托法替布（1mg/kg、3mg/kg、10mg/kg）观察脓毒症大鼠的存活率。结果发现，托法替布（10mg/kg）显著提高了脓毒症大鼠的存活率。我们选择托法替布（10mg/kg），重点研究其对急性肺损伤的保护作用。结果证实，托法替布显著抑制TNF-α、IL-1β、IL-6和IFN-γ等炎症因子的表达，降低脓毒症肺组织的湿干重比，并显著改善肺组织病理损伤。这些结果可能与托法替布对JAK-STAT/NF-κB信号通路的抑制作用有关。综上所述，我们首次发现托法替布对脓毒症诱导的急性肺损伤具有保护作用，它可能是治疗脓毒症急性肺损伤的一种有前景的药物。
