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.

中文翻译：

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Tofacitinib 通过抑制 JAK-STAT/NF-κB 通路减少脓毒症大鼠模型的急性肺损伤并提高存活率

急性肺损伤是脓毒症死亡的主要原因。托法替尼 (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仍不清楚。本研究旨在通过盲肠结扎穿孔法建立大鼠脓毒症模型，评价托法替布对大鼠脓毒症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及可能的作用机制。在本研究中，TOFA（1 mg/kg、3 mg/kg、10 mg/kg）用于观察败血症大鼠的存活率。结果发现，TOFA (10 mg/kg) 显着提高了败血症大鼠的存活率。我们选择了 TOFA (10 mg/kg)，重点研究了 TOFA 对急性肺损伤的保护作用。结果证实，TOFA显着抑制TNF-α、IL-1β、IL-6和IFN-γ炎症因子，降低化脓性肺组织的W/D重量比，显着改善肺组织病理学损伤。这些结果可能与 TOFA 对 JAK-STAT/NF-κ B 信号通路的抑制作用有关。总之，我们首次发现TOFA对脓毒症引起的急性肺损伤具有保护作用，可能是治疗脓毒症急性肺损伤的一种有前途的药物。