超声靶向微泡破坏技术调控星形胶质细胞联合神经干细胞移植对创伤性脑损伤小鼠神经功能修复的实验研究  

Ultrasound-targeted microbubbles destruction technology-mediated astrocytes combined with neural stem cells transplantation for neurological function recovery in traumatic brain injury mice:an experimental study

作　　者：黎清龙 段茂 巩寰 李苇 朱琼 李海艳[1] 唐君辉 徐亚丽 LI Qinglong;DUAN Mao;GONG Huan;LI Wei;ZHU Qiong;LI Haiyan;TANG Junhui;XU Yali(Department of Ultrasound,the Second Affiliated Hospital of Army Medical University,Chongqing 400037,China;Health Team of Shijiazhuang Branch of Hebei Provincial Armed Police Force,Shijiazhuang 050000,China;Department of Ultrasound,the Army 953 Hospital of PLA,Shigatse 857000,China;Department of Ultrasound,Tibet Military Command General Hospital of PLA,Lhasa 850000,China)

机构地区：[1]陆军军医大学第二附属医院超声科,重庆400037 [2]武警河北省总队石家庄市支队卫生队,河北石家庄050000 [3]中国人民解放军陆军第九五三医院超声科,西藏自治区日喀则857000 [4]中国人民解放军西藏军区总医院超声科,西藏自治区拉萨850000

出　　处：《临床超声医学杂志》2025年第2期89-96,共8页Journal of Clinical Ultrasound in Medicine

基　　金：国家自然科学基金面上项目(81971774);重庆市科技局自然科学基金项目(CSTB2022NSCQ-MSX0921)。

摘　　要：目的探讨超声靶向微泡破坏技术(UTMD)调控星形胶质细胞(AS)联合神经干细胞(NSCs)移植在创伤性脑损伤(TBI)小鼠神经功能修复中的应用价值及其作用机制。方法将50只小鼠随机分为对照组、TBI组、UTMD组、UTMD+NSCs组及UTMD+NSCs+AS组,每组各10只,其中对照组为正常小鼠且未进行任何处理;其余各组小鼠使用改良Feeney法建立TBI模型,建模1 d后进行分组治疗,每3天治疗1次,共治疗3次,具体方法:TBI组仅建模,UTMD组接受UTMD开放血脑屏障,UTMD+NSCs组接受UTMD开放血脑屏障联合NSCs移植,UTMD+NSCs+AS组接受UTMD开放血脑屏障联合NSCs和AS移植。于治疗第1、4、8、12天采用改良神经功能损伤程度评分(mNSS)评估神经功能损伤程度;于治疗第12天应用MRI检查各组小鼠脑组织水肿体积;同时采用酶联免疫吸附测定法(ELISA)、逆转录聚合酶链式反应法(RT-PCR)检测各组小鼠脑组织中神经保护因子[脑源性神经营养因子(BDNF)、胶质细胞源性神经营养因子(GDNF)、神经生长因子(NGF)、碱性成纤维细胞生长因子(bFGF)]和神经损伤因子[中枢神经系统特异性蛋白(S100B)、热休克蛋白70(HSP70)、半胱氨酸蛋白酶-3(Caspase-3)]表达水平,比较各组上述检查结果的差异。结果治疗第1、4、8、12天,UTMD+NSCs+AS组、UTMD+NSCs组、UTMD组、TBI组mNSS评分均高于对照组,差异均有统计学意义(均P<0.05)。治疗第1、4天,UTMD+NSCs+AS组、UTMD+NSCs组、UTMD组、TBI组mNSS评分两两比较差异均无统计学意义。治疗第8天,UTMD+NSCs+AS组mNSS评分低于UTMD组、TBI组,差异均有统计学意义(均P<0.05);其余组间两两比较差异均无统计学意义。治疗第12天,UTMD+NSCs+AS组mNSS评分低于UTMD+NSCs组、UTMD组、TBI组,UTMD+NSCs组mNSS评分低于UTMD组、TBI组,差异均有统计学意义(均P<0.05);UTMD组与TBI组比较差异无统计学意义。治疗第12天,TBI组、UTMD组、UTMD+NSCs组、UTMD+NSCs+AS组小鼠脑组织水肿体积分别为Objective To explore the application value and mechanism of action of ultrasound-targeted microbubbles destruction technology(UTMD)-mediated astrocytes(AS)combined with neural stem cells(NSCs)transplantation on neurological function recovery in traumatic brain injury(TBI)mice.Methods A total of 50 mice were randomly divided into 5 groups:control group,TBI group,UTMD group,UTMD+NSCs group and UTMD+NSCs+AS group,with 10 mice in each group.The control group consisted of normal mice that didn’t receive any treatmeat,while the remaining groups were subjected to TBI model using the modified Feeney method.1 d after modeling,the mice were treated according to their respective groups,with treatments administered every 3 d for a total of 3 times.The TBI group only underwent modeling,the UTMD group underwent UTMD blood-brain barrier opening treatment,the UTMD+NSCs group underwent UTMD blood-brain barrier opening treatment combined with NSCs transplantation,and the UTMD+NSCs+AS group underwent UTMD blood-brain barrier opening treatment combined with NSCs and AS transplantation.Neurological dysfunction degree were assessed by the modified neurological severity score(mNSS)on the 1st,4th,8th and 12th after treatment.On the 12th day,MRI was used to measure brain edema volume of brain tissue in each group,and enzyme-linked immunosorbent assay(ELISA)and reverse transcription polymerase chain reaction(RT-PCR)were used to measure neuroprotective factors,including brain-derived neurotrophic factor(BDNF),glial cell-derived neurotrophic factor(GDNF),nerve growth factor(NGF)and basic fibroblast growth factor(bFGF),and neurotoxic factors,including central nervous system-specific protein(S100B),heat shock protein 70(HSP70)and cysteine protease-3(caspase-3)expression levels in brain tissue in all groups.The differences in the above examination results among each group were compared.Results The mNSS scores of the UTMD+NSCs+AS group,UTMD+NSCs group,UTMD group and TBI group were higher than those of the control group on the 1st,4th,8th and

关 键 词：超声靶向微泡破坏技术 星形胶质细胞 神经干细胞 神经功能修复 创伤性脑损伤 小鼠 

分 类 号：R445.1[医药卫生—影像医学与核医学]