Surgical Intensive Care Unit, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, P.R. China.
Mol Med Rep. 2018 Jan;17(1):1717-1723. doi: 10.3892/mmr.2017.8056. Epub 2017 Nov 14.
Pulmonary fibrosis is a chronic, progressive, lethal lung disease characterized by alveolar cell necrosis and dysplasia of interstitial fibrotic tissue, resulting in loss of lung function and eventual respiratory failure. Previously, glucocorticoid drugs were used to treat this lung disorder. However, positive responses were recorded in less than half of treated patients and the cytotoxicity caused by high dosage treatment is still a concern. The present study investigated whether ulinastatin, a typical urinary trypsin inhibitor that mitigates numerous inflammatory responses, could be a treatment option for lung fibrosis. The results demonstrated that ulinastatin had the ability to ameliorate interstitial fibrosis and alveolar exudates and to protect against lung diseases induced by smoke, irradiation or silica particles. The mechanism of ulinastatin resulted in the downregulation of inflammatory cascades: Transforming growth factor‑β1, tumor necrosis factor‑α and nuclear factor‑κB, as demonstrated by western blotting and ELISA. Ulinastatin treatment with a high dose (100,000 U/kg body weight/day) resulted in an attenuated inflammatory response, and inhibited fibrosis formation in lungs, suggesting that ulinastatin may become a part of a clinical therapeutic strategy.
肺纤维化是一种慢性、进行性、致命的肺部疾病，其特征是肺泡细胞坏死和间质纤维组织的异型增生，导致肺功能丧失，最终导致呼吸衰竭。以前，使用糖皮质激素药物来治疗这种肺部疾病。然而，在接受治疗的患者中，不到一半的患者有阳性反应，而且大剂量治疗引起的细胞毒性仍然令人关注。本研究探讨了尿胰蛋白酶抑制剂乌司他丁是否可以作为肺纤维化的治疗选择，因为乌司他丁可以减轻多种炎症反应。结果表明，乌司他丁具有改善间质纤维化和肺泡渗出的能力，并能预防烟雾、辐射或二氧化硅颗粒引起的肺部疾病。乌司他丁通过下调炎症级联反应发挥作用：通过 Western blot 和 ELISA 证实转化生长因子-β1、肿瘤坏死因子-α和核因子-κB。高剂量（100,000 U/kg 体重/天）乌司他丁治疗可减轻炎症反应，抑制肺部纤维化形成，表明乌司他丁可能成为临床治疗策略的一部分。
