Yenepoya Research Centre, Yenepoya University, Deralakatte, Mangalore 575018, Karnataka, India.
Yenepoya Research Centre, Yenepoya University, Deralakatte, Mangalore 575018, Karnataka, India; Rahman Lab, Department of Environmental Medicine, University of Rochester Medical Center, Rochester, NY 14642, United States of America.
Toxicol Appl Pharmacol. 2022 Aug 15;449:116116. doi: 10.1016/j.taap.2022.116116. Epub 2022 Jun 15.
Persistent injuries and chronic inflammation paired with dysregulated healing process in the lungs leads to scarring and stiffening of the tissue leading to a condition called pulmonary fibrosis. There is no efficacious therapy against the condition because of the poorly understood pathophysiology of the disease. Curcumin is well known anti-inflammatory natural compound and is shown to have beneficial effects in many diseases. It is also reported to show antifibrotic activities in pulmonary fibrosis. There are evidences that fibrinolytic system plays a crucial role in the development of pulmonary fibrosis. We aimed to see whether curcumin could regulate inflammation and fibrinolysis in murine model of pulmonary fibrosis. We prepared BLM induced pulmonary fibrosis model by administering BLM at a dose of 2 mg/ kg bodyweight. Curcumin (75 mg/kg body wt) was instilled intraperitoneally on different time points. The effect of curcumin on inflammatory cytokines and fibrinolytic system was studied using molecular biology techniques like RT-PCR, western blot and immunohistochemistry/immunofluorescence. We observed that BLM brought changes in the expressions of components in the fibrinolytic system, i.e. BLM favoured fibrin deposition by increasing the expression of PAI-1 (plasminogen activator inhibitor) and decreasing the expression of uPA (Urokinase plasminogen activator) and uPAR (Urokinase plasminogen activator receptor). We also demonstrate that curcumin could restore the normal expression of fibrinolytic components, uPA, uPAR and PAI-1. Curcumin could also minimize the expression of key enzymes in tissue remodeling in pulmonary fibrosis, MMP-2 and MMP-9, which were elevated in the BLM treated group. Our data suggest that curcumin exerts an anti-inflammatory and antifibrotic effect in lungs. We highlight curcumin as a feasible adjuvant therapy option against pulmonary fibrosis.
肺部持续损伤和慢性炎症加上失调的愈合过程导致组织瘢痕和僵硬，从而导致一种称为肺纤维化的疾病。由于对该疾病病理生理学的了解不足，目前尚无有效的治疗方法。姜黄素是一种众所周知的抗炎天然化合物，已被证明对许多疾病具有有益的作用。它也被报道在肺纤维化中具有抗纤维化作用。有证据表明，纤维蛋白溶解系统在肺纤维化的发展中起着至关重要的作用。我们旨在观察姜黄素是否可以调节博莱霉素诱导的肺纤维化小鼠模型中的炎症和纤维溶解。我们通过给予 BLM 2mg/kg 体重来制备 BLM 诱导的肺纤维化模型。姜黄素（75mg/kg 体重）在不同时间点通过腹腔内给药。使用 RT-PCR、Western blot 和免疫组织化学/免疫荧光等分子生物学技术研究姜黄素对炎症细胞因子和纤维溶解系统的影响。我们观察到 BLM 引起纤维溶解系统成分表达的变化，即 BLM 通过增加 PAI-1（纤溶酶原激活物抑制剂）的表达和降低 uPA（尿激酶纤溶酶原激活物）和 uPAR（尿激酶纤溶酶原激活物受体）的表达来促进纤维蛋白沉积。我们还证明姜黄素可以恢复纤维溶解成分 uPA、uPAR 和 PAI-1 的正常表达。姜黄素还可以最大限度地减少组织重塑中关键酶 MMP-2 和 MMP-9 在肺纤维化中的表达，这些酶在 BLM 处理组中升高。我们的数据表明，姜黄素在肺部发挥抗炎和抗纤维化作用。我们强调姜黄素作为一种可行的治疗肺纤维化的辅助治疗选择。
