补骨脂素调控Keap1/Nrf2通路减轻丙泊酚诱导的幼龄大鼠神经毒性  

Psoralen attenuates propofol-induced neurotoxicity in young rats by regulating the Keap1/Nrf2 pathway

作　　者：陈宇 刘文家 李志鹏 杨永锦 CHEN Yul;LIU Wenjia;LI Zhipeng;YANG Yongjin(Department of Anesthesiology,Changle County Qicheng Traditional Chinese Medicine Hospital,Weifang,Shandong 262400,China;Department of Anesthesiology,Sunshine Union Hospital,Weifang,Shandong 261000,China;Department of Anesthesiology,Changle People's Hospital,Weifang,Shandong 262400,China)

机构地区：[1]昌乐齐城中医院麻醉科,山东潍坊262400 [2]阳光融和医院麻醉科,山东潍坊261000 [3]昌乐县人民医院麻醉科,山东潍坊262400

出　　处：《中国优生与遗传杂志》2024年第4期686-693,共8页Chinese Journal of Birth Health & Heredity

基　　金：潍坊市科技发展计划项目申报书(2019YX115)。

摘　　要：目的探讨补骨脂素对幼龄大鼠神经毒性的保护作用及机制。方法采用100μmol/L丙泊酚孵育海马细胞系HT22细胞6h诱导细胞炎性,设置对照组、丙泊酚组、丙泊酚+补骨脂素(1、5、10μmol/L)组、丙泊酚+补骨脂素(10μmol/L)+Keap1/Nrf2通路抑制剂(KI696,5μmol/L)组。CCK8试验检测细胞活力,流式细胞术检测凋亡。幼龄SD大鼠随机分为对照组(C组)、丙泊酚组(P组)、丙泊酚+补骨脂素组(PP组)、丙泊酚+补骨脂素+KI696组(PPI组)。P组大鼠腹腔注射丙泊酚50 mg/kg,PP组注射丙泊酚和补骨脂素20 mg/kg,PPI组注射丙泊酚、补骨脂素和KI69630μmol/kg。采用Nissl染色观察海马组织病理结构变化,ELISA法检测细胞和组织炎症反应(IL-6和TNF-α水平)和氧化应激(MDA含量、SOD和GSH活性),Westernblot检测Keap1和Nrf2蛋白表达。结果与对照组相比较,丙泊酚组HT22细胞活力明显降低,细胞凋亡、Keap1蛋白水平、炎症和氧化应激显著升高(P<0.05);补骨脂素以剂量依赖的形式改善细胞神经炎症和氧化应激(P<0.05),KI696处理可逆转补骨脂素对细胞功能的保护作用。与C组比较,P组大鼠海马组织炎症和氧化应激加重。补骨脂素处理减轻了大鼠海马组织神经元受损。结论补骨脂素治疗可激活Keap1/Nrf2通路缓解丙泊酚诱导的幼龄大鼠神经毒性。Objective To investigate the protective effects and mechanisms of psoralen on neurotoxicity in juvenile rats.Methods Hippocampal cell line HT22 cells were incubated with 100μmol/L propofol for 6 hours to induce cell inflammation.The experiment included control group,propofol group,propofol+psoralen(1,5,10μmol/L)groups,and propofol+psoralen(10μmol/L)+Keap1/Nrf2 pathway inhibitor(KI696,5μmol/L)group.Cell viability was tested by CCK8 assay,and apoptosis was detected by flow cytometry.Juvenile SD rats were randomly divided into control group(C group),propofol group(P group),propofol+psoralen group(PP group),and propofol+psoralen+KI696 group(PPI group).P group rats were intraperitoneally injected with propofol 50 mg/kg,PP group with propofol and psoralen 20 mg/kg,and PPI group with propofol,psoralen,and KI69630μmol/kg.Hippocampal tissue pathological changes were observed using Nissl staining.Inflammatory responses(IL-6 and TNF-αlevels)and oxidative stress(MDA content,SOD,and GSH activity)in cells and tissues were measured by ELISA,and Keap1 and Nrf2 protein expression was detected by Western blot.Results Compared to the control group,the HT22 cell viability in the propofol-treated group was significantly reduced,and cell apoptosis,Keap1 protein level,inflammatory response and oxidative stress were significantly increased(P<0.05).Psoralen treatment improved cell neuroinflammation and oxidative stress in a dose-dependent manner(P<0.05),and KI696 treatment reversed the protective effects of psoralen on cell functions.Compared to the C group,hippocampal inflammation and oxidative stress in the P group rats worsened.Psoralen treatment alleviated neuronal damage in rat hippocampal tissue.Conclusion Psoralen alleviates propofol-induced neurotoxicity in young rats by activating the Keap1/Nrf2 pathway.

关 键 词：补骨脂素 丙泊酚 Keap1/Nrf2通路 神经毒性 

分 类 号：R285.5[医药卫生—中药学]