Sung Jun-Seok, Ko Il-Gyu, Hwang Lakkyong, Kim Sang-Hoon, Han Jin Hee, Jeon Jung Won, Kim Sae Rom, Lee Jeong Mi, Choi Cheon Woong
Department of Physiology, College of Medicine, Kyung Hee University, Seoul 02447, Republic of Korea.
Research Support Center, School of Medicine, Keimyung University, Deagu 42601, Republic of Korea.
Biomedicines. 2025 Apr 17;13(4):989. doi: 10.3390/biomedicines13040989.
Increased exposure to particulate matter (PM) from air pollution causes lung inflammation and increases morbidity and mortality due to respiratory diseases. Pirfenidone is an anti-fibrotic agent used to treat idiopathic pulmonary fibrosis. : In this experiment, we studied the therapeutic effects of pirfenidone on PM-induced pulmonary fibrosis. : Pulmonary fibrosis was induced by the intratracheal application of 100 μg/kg PM10 mixed with 200 μL saline. After 42 days of PM10 infusion, 0.2 mL of distilled water with pirfenidone was orally administered to the pirfenidone-treated groups (200 and 400 mg/kg) every other day for a total of 15 times over 30 days. : The intratracheal administration of PM resulted in lung injury and a significant decrease in the number of bronchoalveolar lavage fluid cells. PM administration increased the lung injury score, level of lung fibrosis, and production of pro-inflammatory cytokines. Pirfenidone treatment effectively suppressed transforming growth factor-β-activated kinase 1 in PM-induced pulmonary fibrosis. The present changes inhibited the expressions of mitogen-activated protein kinase kinase 3 and p38, which suppressed transforming growth factor-β, ultimately alleviating lung fibrosis. PM exposure upregulated the expressions of fibronectin and type 1 collagen. PM exposure enhanced connective tissue growth factor and hydroxyproline levels in the lung tissue. The levels of these fibrosis-related factors were inhibited by pirfenidone treatment. : These results suggest that pirfenidone is therapeutically effective against PM-induced pulmonary fibrosis.
空气污染导致的颗粒物（PM）暴露增加会引发肺部炎症，并增加呼吸系统疾病的发病率和死亡率。吡非尼酮是一种用于治疗特发性肺纤维化的抗纤维化药物。在本实验中，我们研究了吡非尼酮对PM诱导的肺纤维化的治疗效果。通过气管内注入100μg/kg PM10与200μL生理盐水混合液诱导肺纤维化。在注入PM10 42天后，每隔一天给吡非尼酮治疗组（200和400mg/kg）口服0.2mL含吡非尼酮的蒸馏水，共30天，总计15次。气管内注入PM导致肺损伤以及支气管肺泡灌洗液细胞数量显著减少。注入PM增加了肺损伤评分、肺纤维化水平以及促炎细胞因子的产生。吡非尼酮治疗有效抑制了PM诱导的肺纤维化中转化生长因子-β激活激酶1。目前的变化抑制了丝裂原活化蛋白激酶激酶3和p38的表达，从而抑制了转化生长因子-β，最终减轻了肺纤维化。PM暴露上调了纤连蛋白和I型胶原的表达。PM暴露提高了肺组织中结缔组织生长因子和羟脯氨酸水平。这些纤维化相关因子的水平通过吡非尼酮治疗得到抑制。这些结果表明吡非尼酮对PM诱导的肺纤维化具有治疗效果。
