右美托咪定对脑出血大鼠铁死亡及HO-1表达的影响  

Effects of dexmedetomidine on the iron death and HO-1 expression in rats with cerebral hemorrhage

作　　者：邢丹丹 张敏[1] 李铁军[1] 张文奇 宁巧明[1] 吴多志[1] 王志华[1] XING Dandan;ZHANG Min;LI Tiejun(Department of Anesthesiology,Hainan Provincial People’s Hospital,Hainan,Haikou 570311,China)

机构地区：[1]海南省人民医院麻醉科,海口市570311

出　　处：《河北医药》2023年第1期5-10,共6页Hebei Medical Journal

基　　金：海南省科学技术厅资助项目(编号:2019RC365)。

摘　　要：目的评价右美托咪定对脑出血大鼠铁死亡的影响,并从血红酶素加氧酶-1(HO-1)介导的铁代谢途径探讨其作用机制。方法取SD大鼠建立大鼠脑出血模型,分为假手术组、模型组、右美托咪定组、去铁胺组、HO-1激活剂组、右美托咪定+HO-1激活剂组,每组20只。6组干预结束后,进行神经功能缺损评分;取血肿周围组织,HE染色及TUNEL染色检测神经元形态及凋亡;普鲁士蓝染色观察检测铁沉积量;试剂盒法检测“铁死亡”相关因子[丙二醛(MDA)、谷胱甘肽(GSH)及谷胱甘肽还原酶4(GPX4)]水平;Western blot法检测HO-1、“铁死亡”主要标志物[环氧合酶-2(COX-2)、血红素转运蛋白(HPC1)、二价金属转运体(DMT1)、转铁蛋白受体(TfR)、铁调节蛋白-1(IRP-1)、铁调素(Hepcidin)、铁输出蛋白(FPN1)]表达。结果与假手术组比较,模型组大鼠神经功能缺损评分降低,血肿周围组织神经元损伤、凋亡严重,铁沉积、铁离子含量及铁死亡升高,HO-1活化介导的铁摄取、转运及输入等活性升高,铁输出活性降低(P<0.05)。右美托咪啶及去铁胺干预均可降低血肿周围组织铁沉积,抑制HO-1活化介导的铁摄取、转运、输入、输出等代谢活性异常,缓解神经系统损伤(P<0.05)。HO-1激活剂可进一步促进HO-1活化介导的铁代谢异常,加重铁沉积及铁死亡,并逆转右美托咪啶发挥的抗“铁死亡”及抗神经系统损伤作用(P<0.05)。结论右美托咪定可改善脑出血大鼠“铁死亡”及神经功能缺损症状,且其改善作用可能与阻断HO-1通路活化介导的铁代谢异常有关。Objective To investigate the effects of dexmedetomidine on the iron death and HO-1 expression in rats with cerebral hemorrhage, and to explore its action mechanism through the iron metabolism pathway mediated by heme oxygenase-1(HO-1).Methods A total of 120 SD rats were used to establishe the animal models with cerebral hemorrhage, who were divided into sham operation group, model group, dexmedetomidine group, deferoxamine group, HO-1 activator group, dexmedetomidine+HO-1 activator group, with 20 rats in each group.After the intervention, the neurological deficit was scored, and the tissues around the hematoma were taken out, and HE staining and TUNEL staining were used to detect neuron morphology and apoptosis;prussian blue staining was used to detect the amount of iron deposits;the kit method was used to detect the levels of “iron death” related factors including malondialdehyde(MDA),glutathione(GSH) and glutathione reductase 4(GPX4);Western Blot was used to detect the expression levels of HO-1,the main markers of “iron death”-cyclooxygenase-2(COX-2),heme carrier protein 1(HPC1),divalent metal transporter(DMT1),transferrin receptor(TfR),iron regulatory protein-1(IRP-1),Hepcidin as well as FPN1.Results Compared with those in sham operation group, the neurological deficit scores in model group were decreased, and the neuron damage and apoptosis of the tissue around the hematoma were severe, and the iron deposition, iron ion content and iron death were increased, and HO-1 activation-mediated iron uptake, transport and import activities were increased, and the activity of iron export was significantly decreased(P<0.05).The intervention of dexmedetomidine and deferoxamine could decrease the iron deposition in the tissues around the hematoma, inhibit the abnormal metabolic activity such as iron uptake, transport, import, and export mediated by HO-1 activation, so as to relieve the nervous system damage(P<0.05).HO-1 activator could further promote the abnormal iron metabolism mediated by HO-1 activation, aggra

关 键 词：右美托咪定 脑出血 铁死亡 血红酶素加氧酶-1 

分 类 号：R743.34[医药卫生—神经病学与精神病学]