急性呼吸窘迫综合征(ARDS)是急性发作,患者表现为弥漫性肺泡损伤,难治性低氧血症,和非心源性肺水肿。ARDS进展到最初的渗出阶段,炎症阶段,和最后的纤维化阶段。吡非尼酮,一种强大的抗纤维化药物,被称为抑制特发性肺纤维化中纤维化进展的药物。在这项研究中,我们用大鼠研究了吡非尼酮对脂多糖(LPS)和博来霉素诱导的ARDS的治疗效果。通过气管内给予溶解在0.2mL生理盐水中的3mg/kg的LPS和3mg/kg的博来霉素来创建ARDS大鼠模型。吡非尼酮治疗组每2天10次口服100或200mg/kg溶于0.5mL蒸馏水中的吡非尼酮,共20天。气管内施用LPS和博来霉素增加肺损伤评分并显著产生促炎细胞因子。ARDS诱导增加了转化生长因子(TGF)-β1/Smad-2信号因子的表达。此外,基质金属蛋白酶(MMP)-9/组织金属蛋白酶抑制剂(TIMP)-1发生失衡,导致纤维化相关因子增强。与未治疗组相比,吡非尼酮治疗强烈抑制了TGF-β1/Smad-2信号因子的表达,并改善了MMP-9/TIMP-1的失衡。这些作用导致纤维化因子和促炎细胞因子的减少,促进受损肺组织的恢复。该研究的这些结果表明吡非尼酮给药抑制ARDS动物模型中的炎症和纤维化。因此,吡非尼酮可以被认为是ARDS的一种新的早期治疗方法。
Acute respiratory distress syndrome (ARDS) occurs as an acute onset condition, and patients present with diffuse alveolar damage, refractory hypoxemia, and non-cardiac pulmonary edema. ARDS progresses through an initial exudative phase, an inflammatory phase, and a final fibrotic phase. Pirfenidone, a powerful anti-fibrotic agent, is known as an agent that inhibits the progression of fibrosis in idiopathic pulmonary fibrosis. In this study, we studied the treatment efficiency of pirfenidone on lipopolysaccharide (LPS) and bleomycin-induced ARDS using rats. The ARDS rat model was created by the intratracheal administration of 3 mg/kg LPS of and 3 mg/kg of bleomycin dissolved in 0.2 mL of normal saline. The pirfenidone treatment group was administered 100 or 200 mg/kg of pirfenidone dissolved in 0.5 mL distilled water orally 10 times every 2 days for 20 days. The administration of LPS and bleomycin intratracheally increased lung injury scores and significantly produced pro-inflammatory cytokines. ARDS induction increased the expressions of transforming growth factor (TGF)-β1/Smad-2 signaling factors. Additionally, matrix metalloproteinase (MMP)-9/tissue inhibitor of metalloproteinase (TIMP)-1 imbalance occurred, resulting in enhanced fibrosis-related factors. Treatment with pirfenidone strongly suppressed the expressions of TGF-β1/Smad-2 signaling factors and improved the imbalance of MMP-9/TIMP-1 compared to the untreated group. These effects led to a decrease in fibrosis factors and pro-inflammatory cytokines, promoting the recovery of damaged lung tissue. These results of this study showed that pirfenidone administration suppressed inflammation and fibrosis in the ARDS animal model. Therefore, pirfenidone can be considered a new early treatment for ARDS.