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.

这项研究旨在调查酪氨酸激酶抑制剂达沙替尼（DAS）对大鼠单侧输尿管梗阻（UUO）诱发的肾纤维化的肾脏保护作用。DAS给药改善了肾功能，减轻了肾脏氧化应激，同时使结扎的肾脏质量指数降低，肾脏组织病理学改变显着回缩，并抑制了肾间质纤维化。然而，DAS给药减弱了肾脏的磷酸化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因子3（p-STAT）的肾脏表达。 -3）/ STAT-3与肿瘤坏死因子-α（TNF-α），白介素-1β（IL-1β）和单核细胞趋化蛋白-1（MCP-1）的肾脏含量平行降低。DAS减少了间质巨噬细胞浸润，降低了肾纤维化转化生长因子-β1（TGF-β1）的水平，并抑制了肾α-平滑肌肌动蛋白（α-SMA）和纤连蛋白的间质表达。总体而言，DAS可能通过减轻肾脏氧化应激，削弱Src / STAT-3 /NF-κB信号传导和减轻肾脏炎症而减慢了肾间质纤维化的进程。