摘要
目的:研究右美托咪定(DEX)通过调节磷脂酰肌醇3-激酶(PI3K)/蛋白激酶B(Akt)/核因子E2相关因子2(Nrf2)信号通路改善胸部创伤大鼠肺组织损伤的作用机制。方法:将雄性SD大鼠分为对照组、模型组、DEX低剂量(DEX-L,10μg·kg^(-1)·d^(-1))组、DEX高剂量(DEX-H,50μg·kg^(-1)·d^(-1))组、DEX高剂量+LY294002(DEX-H+LY,50μg·kg^(-1)·d^(-1)DEX+5 mg·kg^(-1)·d^(-1)PI3K抑制剂LY294002)组。比值法测定大鼠肺指数,测定肺湿/干重比值,ELISA测定大鼠肺泡灌洗液内炎症因子水平,H-E染色观察肺组织病理,免疫印迹检测PI3K/Akt/Nrf2通路蛋白表达。结果:相较于对照组,模型组大鼠肺组织存在炎性浸润,排列松散,肺泡壁变厚,肺指数、肺湿/干重比、白细胞介素(IL)1-β(IL-1β)、IL-6与肿瘤坏死因子α(TNF-α)水平以及炎症评分显著升高,PI3K、Akt与Nrf2蛋白表达下降;相较于模型组,DEX-L组、DEX-H组大鼠肺组织损伤减轻,大鼠肺指数、肺湿/干重比、肺泡灌洗液IL-1β、IL-6、TNF-α水平、炎症评分降低,PI3K、Akt、Nrf2蛋白表达显著升高;相较于DEX-H组,DEX-H+LY组大鼠肺组织损伤加重,肺指数、肺湿/干重比、肺泡灌洗液IL-1β、IL-6、TNF-α水平以及炎症评分升高,PI3K、Akt、Nrf2表达降低。结论:DEX可能通过激活PI3K/Akt/Nrf2信号通路改善胸部创伤大鼠肺组织损伤。
Objective:To investigate the mechanism by which dexmedetomidine(DEX)improves lung tissue injury in rats with thoracic trauma by regulating the PI3K/Akt/Nrf2 signaling pathway.Methods:Male Sprague Dawley rats were randomly grouped into control group,model group,low-dose DEX(DEX-L,10μg·kg^(-1)·d^(-1) DEX)group,high-dose DEX(DEX-H,50μg·kg^(-1)·d^(-1) DEX)group,and high-dose DEX+LY294002(DEX-H+LY,50μg·kg^(-1)·d^(-1) DEX+5 mg·kg^(-1)·d^(-1) PI3K inhibitor LY294002)group.The ratio method was applied to determine the lung index of rats.The wet/dry weight ratio of the lungs was measured.ELISA was used to measure the inflammatory factor levels in rat bronchoalveolar lavage fluid.H-E staining was applied to determine pulmonary histopathology.Western blotting was applied to determine the expression of PI3K/Akt/Nrf2 pathway proteins.Results:Compared with the control group,the lung tissue of the model group rats showed inflammatory infiltration,loose arrangement,and thickening of alveolar walls,with the lung index,lung wet/dry weight ratio,levels of IL-1β,IL-6,TNF-αin bronchoalveolar lavage fluid,and inflammation score increased,while the expression of PI3K,Akt,and Nrf2 proteins decreased.Compared with the model group,the DEX-L and DEX-H groups showed reduced lung tissue injury in rats,with the lung index,lung wet/dry weight ratio,levels of IL-1β,IL-6,TNF-αin bronchoalveolar lavage fluid,and inflammation score decreased,while the expression of PI3K,Akt,and Nrf2 increased.Compared with the DEX-H group,the lung tissue injury in the DEX-H+LY group worsened,with the lung index,lung wet/dry weight ratio,levels of IL-1β,IL-6,TNF-αin bronchoalveolar lavage fluid,and inflammation score increased,while the expression of PI3K,Akt,and Nrf2 decreased.Conclusion:DEX may improve lung tissue injury in rats with thoracic trauma by activating the PI3K/Akt/Nrf2 signaling pathway.
作者
徐双婷
许舒
罗璇
Xu Shuangting;Xu Shu;Luo Xuan(Department of Anesthesiology,Lengshuitan Campus,Yongzhou Central Hospital,Yongzhou 425000,China)
出处
《解剖学杂志》
2025年第4期299-302,332,共5页
Chinese Journal of Anatomy
