This research aimed to investigate the reno-protective impact of the tyrosine kinase inhibitor dasatinib (DAS) against renal fibrosis induced by unilateral ureteral obstruction (UUO) in rats. DAS administration improved renal function and mitigated renal oxidative stress with paralleled reduction in the ligated kidney mass index, significant retraction in renal histopathological alterations and suppression of renal interstitial fibrosis. Nevertheless, DAS administration attenuated renal expression of phosphorylated Src (p-Src), Abelson (c-Abl) tyrosine kinases, nuclear factor-kappaB (NF-κB) p65, and phosphorylated signal transducer and activator of transcription-3 (p-STAT-3)/STAT-3 with paralleled reduction in renal contents of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and monocyte chemoattractant protein-1 (MCP-1). DAS diminished interstitial macrophage infiltration and decreased renal profibrotic transforming growth factor-β1 (TGF-β1) levels and suppressed interstitial expression of renal α-smooth muscle actin (α-SMA) and fibronectin. Collectively, DAS slowed the progression of renal interstitial fibrosis, possibly via attenuating renal oxidative stress, impairing Src/STAT-3/NF-κB signaling, and reducing renal inflammation.

本研究旨在探讨酪氨酸激酶抑制剂达沙替尼（DAS）对单侧输尿管梗阻（UUO）引起的大鼠肾纤维化的保护作用。 DAS 给药改善了肾功能，减轻了肾脏氧化应激，同时降低了结扎肾质量指数，显着缩小了肾组织病理学改变并抑制了肾间质纤维化。然而，DAS 给药减弱了磷酸化 Src (p-Src)、Abelson (c-Abl) 酪氨酸激酶、核因子-κB (NF-κB) p65 以及磷酸化信号转导子和转录激活子 3 (p-STAT) 的肾脏表达。 -3)/STAT-3 与肾肿瘤坏死因子-α (TNF-α)、白细胞介素-1β (IL-1β) 和单核细胞趋化蛋白-1 (MCP-1) 含量平行降低。 DAS 减少间质巨噬细胞浸润，降低肾促纤维化转化生长因子-β1 (TGF-β1) 水平，并抑制肾 α-平滑肌肌动蛋白 (α-SMA) 和纤连蛋白的间质表达。总的来说，DAS 可能通过减弱肾脏氧化应激、损害 Src/STAT-3/NF-κB 信号传导和减少肾脏炎症来减缓肾间质纤维化的进展。