脓毒症会引起脑功能障碍，因此仍然需要一种可行的恢复方法。本研究旨在探讨达沙替尼在内毒素血症期间调节促炎介质、减弱神经炎症反应及其信号通路中的作用。 将 24 只成年雄性瑞士白化小鼠随机分为四组：假手术组（不进行盲肠结扎进行剖腹手术，穿刺、脓毒症（盲肠结扎和穿刺的剖腹术）、载体二甲基亚砜、达沙替尼（20 mg/kg/天）腹膜内注射用于评估白细胞介素 (IL)-6、IL-1β、肿瘤坏死因子-α。 (TNF-α)、IL-10、Toll 样受体 4 (TLR4)、蛋白激酶 B (AKT)、磷酸肌醇 3-激酶 (PI3K)、信号转导子和转录激活子 3 (STAT3) 以及组织病理学检查。 脑脓毒症组中 TNF-α、IL-6 和 IL1β 的组织水平高于假手术组和媒介物组，达沙替尼组的这些标志物的组织水平显着降低，而 IL-10 的组织水平显着高于对照组。败血症和车辆组。假手术组的 TLR4、AKT、STAT3 和 PI3k 组织值比脓毒症组和媒介物组低得多。此外，达沙替尼组中这些标志物的组织水平显着低于脓毒症组和媒介物组。组织病理学表明，与败血症和显示广泛脑部炎症和损伤的媒介物组相比，达沙替尼可以显着减轻脑部损伤和神经炎症的强度。达沙替尼通过调节 TLR4、PI3K、AKT 和STAT3 下游信号通路。版权所有：© 2024 Research in Pharmaceutical Sciences。

Sepsis induces brain dysfunction and there is still a requirement for an unemployed viable restorative approach. This study aimed to investigate the role of dasatinib in the modulation of proinflammatory mediators, attenuating neuroinflammatory response, and it's signaling pathway during endotoxemia.Twenty-four adult male Swiss-albino mice were randomized into four groups: sham (undergo laparotomy without cecal ligation and puncture, sepsis (laparotomy with cecal ligation and puncture), vehicle-dimethyl sulfoxide, dasatinib (20 mg/kg/day) intraperitoneally. Brain tissue used for assessment of interleukin (IL)-6, IL-1β, tumor necrosis factor-alpha (TNF-α), IL-10, Toll-like receptor 4 (TLR4), protein kinase B (AKT), phosphoinositide 3-kinases (PI3K), signal transducer and activator of transcription 3 (STAT3), and histopathological examination.Brain tissue levels of TNF-α, IL-6, and IL1 β were higher in the sepsis group than in the sham and vehicle groups. The dasatinib group had considerably lower tissue levels of these markers and significantly higher tissue values of IL-10 than the sepsis and vehicle groups. The sham group had much lower tissue values of TLR4, AKT, STAT3, and PI3k than in sepsis and vehicle groups. Furthermore, tissue levels of these markers in the dasatinib group were considerably lower than those in the sepsis and vehicle groups. Histopathology demonstrated that dasatinib might considerably reduce brain damage and the intensity of neuroinflammation when compared to sepsis and vehicle groups that showed extensive brain inflammation and damage.Dasatinib attenuated endotoxemia-induced acute brain damage in mice via modulating effects on TLR4, PI3K, AKT, and STAT3 downstream signaling pathways.Copyright: © 2024 Research in Pharmaceutical Sciences.