Effect and mechanism of Nintedanib on acute and chronic radiation-induced lung injury in mice.

Abstract

ObjectiveTo investigate the efficacy of Nintedanib in treating acute and chronic radiation-induced lung injury and its mechanism of action.MethodsA radiation-induced lung injury model was established in mice using 6MV X-rays at 18Gy to irradiate the lungs. The mice were randomly divided into four groups: control group, radiation therapy group, low-dosage Nintedanib + radiation therapy group, and high dosage Nintedanib + radiation therapy group. The mice were euthanized on day 14 and 3 months post-radiation to observe changes in acute and chronic inflammation and the expression of related proteins.ResultsCompared to the radiation therapy group, the low and high-dosage Nintedanib groups showed varying degrees of improvement in mental state, responsiveness, food and water intake, and fur condition. During the acute inflammatory phase, HE staining revealed inflammatory changes in the lung tissues of both Nintedanib groups, but the pathology was less severe than in the radiation group, with the high-dosage group showing more significant reduction. Serum levels of IL-6, TNF-α and TGF-β1 were significantly reduced (P Conclusion(1) Nintedanib can improve the general condition of mice with acute and chronic radiation-induced lung injury and reduce pathological damage to lung tissue. (2) Nintedanib may exert a protective effect on mice with acute and chronic radiation-induced lung injury by downregulating the TGF-β1/Smad2 signaling pathway, thereby inhibiting inflammatory and fibrotic responses.