靶向TRIM63调节氧化应激通路改善急性脑卒中后血脑屏障损伤和神经功能恢复  

Targeting TRIM63 to regulate oxidative stress pathways and improve blood-brain barrier injury and neurological recovery after acute stroke

作　　者：周静[1] 温昌明[1] 高军 张东焕 余洋 汪宁[1] 张在行 张保朝[1] ZHOU Jing;WEN Changming;GAO Jun(Department of Neurology,Nanyang Central Hospital,Nanyang 473000,China)

机构地区：[1]南阳市中心医院神经内科,河南南阳473000

出　　处：《中风与神经疾病杂志》2024年第9期806-810,共5页Journal of Apoplexy and Nervous Diseases

基　　金：河南省重点研发与推广专项(科技攻关)(202102310079)。

摘　　要：目的 观察靶向TRIM63调节氧化应激通路改善急性脑卒中后血脑屏障损伤和神经功能恢复的研究。方法 取成年雄性C57小鼠,随机分为:Sham组,Vehicle组,Myomed-205组,构造短暂性大脑中动脉闭塞(tMCAO)小鼠模型,Myomed-205组、Vehicle组和Sham组分别于拔出线栓后腹腔注射TRIM63抑制剂Myomed-205和等体积溶剂。再灌注3 d观察各组小鼠TTC染色分析脑梗死体积,神经功能评分观察神经功能恢复情况,干湿重法分析脑含水量。ROS、超氧化物歧化酶、谷胱甘肽和丙二醛试剂盒分析各组小鼠脑氧化应激指标含量。Evans Blue法检测血脑屏障损伤情况,Western blotting法观察ZO-1、Occludin蛋白表达情况。结果 发现Myomed-205处理组小鼠与Vehicle组相比脑梗死体积明显降低(P<0.05),100 mg/ml的Myomed-205处理组小鼠比对照组神经功能评分显著降低(P<0.05),而脑含水量比对照组显著降低(P<0.05)。Myomed-205组小鼠在卒中后3 d、7 d、14 d ROS阳性细胞数比Vehicle组显著降低(P<0.05),促氧化应激指标MDA表达量比对照组显著降低(P<0.05),而抗氧化指标GSH、SOD表达量比对照组显著升高(P<0.05)。Myomed-205组小鼠比Vehicle组在卒中后7 d、14 d EB漏出显著降低(P<0.05),ZO-1和Occludin蛋白表达显著升高(P<0.05)。结论 抑制TRIM63信号通路促进小鼠脑缺血性卒中神经功能恢复,此过程可能通过减轻氧化应激反应和血脑屏障损伤完成。Objective To investigate the effect of targeting TRIM63 in regulating oxidative stress pathways and im-proving blood-brain barrier injury and neurological recovery after acute stroke.Methods Adult male C57 mice were ran-domly divided into Sham group,Vehicle group,and Myomed-205 group,and a mouse model of transient middle cerebral artery occlusion(tMCAO)was constructed.After removal of the suture,the mice in the Myomed-205 group and the Ve-hicle group were given intraperitoneal injection of TRIM63 inhibitor,and those in the Sham group were given intraperito-neal injection of an equal volume of solvent.On day 3 of reperfusion,TTC staining was used to observe cerebral infarct vol-ume,neurological score was used to evaluate neurological recovery,and the dry-wet weight method was used to measure brain water content.Reactive oxygen species(ROS),superoxide dismutase(SOD),glutathione(GSH),and malondial-dehyde(MDA)kits were used to measure the content of oxidative stress indices in brain.The Evans Blue method was used to observe blood-brain barrier injury,and Western blotting was used to measure the protein expression levels of ZO-1 and Occludin.Results Compared with the Vehicle group,the Myomed-205 group had a significant reduction in cerebral infarct volume(P<0.05),and compared with the control group,the 100 mg/ml Myomed-205 treatment group had signifi-cant reductions in neurological score(P<0.05)and brain water content(P<0.05).Compared with the Vehicle group,the Myomed-205 group had a significant reduction in the number of ROS-positive cells on days 3,7,and 14 after stroke(P<0.05),and compared with the control group,the Myomed-205 group had a significant reduction in the expression level of the pro-oxidative stress index MDA(P<0.05)and significant increases in the expression levels of the antioxidant indices GSH and SOD(P<0.05).Compared with the Vehicle group,the Myomed-205 group had a significant reduction in EB leakage on days 7 and 14 after stroke(P<0.05)and significant increases in the protein expression levels of

关 键 词：TRIM63 氧化应激 血脑屏障 脑卒中 

分 类 号：R743[医药卫生—神经病学与精神病学]