静脉移植人脂肪间充质干细胞治疗大鼠颅脑损伤  

Treatment of traumatic brain injury in rats with intravenous transplantation of adipose-derived stem cells

作　　者：张天祥[1,2] 杨波[1,2] 关方霞[3] 胡祥[4,5] 杜英[6] 乔晓俊[1] 田毅[1] 巴云涛[1] 段小兵[1] 邓晓辉[1] 谷晨熙[7] 郑文迪[7] 

机构地区：[1]郑州大学第一附属医院神经外科,河南省郑州市450052 [2]河南省高等学校临床医学重点学科开放实验室,河南省郑州市450052 [3]郑州大学生物工程系,河南省郑州市450001 [4]江苏省干细胞与生物治疗公共技术服务平台,江苏省泰州市225300 [5]深圳市北科细胞工程研究所,广东省深圳市518000 [6]郑州大学基础医学院微生物与免疫学教研室,河南省郑州市450052 [7]郑州大学临床医学系,河南省郑州市450001

出　　处：《中国组织工程研究与临床康复》2011年第14期2551-2556,共6页Journal of Clinical Rehabilitative Tissue Engineering Research

基　　金：郑州大学211三期建设项目"干细胞基础与临床研究";江苏省干细胞与生物治疗公共技术服务平台(BM2008146)~~

摘　　要：背景:动物实验及临床研究证实间充质干细胞对创伤性脑损伤具有一定的治疗作用。目的:观察脂肪间充质干细胞移植治疗急性创伤性脑损伤大鼠行为学及损伤脑组织中胶质纤维酸性蛋白、神经元特异性烯醇化酶和巢蛋白的表达。方法:以自由落体硬膜外撞击法制作SD大鼠脑损伤模型后随机分为3组:移植组于脑损伤48h时经尾静脉注射Brdu标记的成人脂肪间充质干细胞;对照组不作处理;生理盐水组于脑损伤48h时经尾静脉注射生理盐水。采用NSS评分法评价大鼠神经功能恢复情况;倒置显微镜观察脂肪间充质干细胞在损伤脑组织内的迁移情况;免疫组织化学法检测大鼠受损脑组织中胶质纤维酸性蛋白、神经元特异性烯醇化酶和巢蛋白表达。结果与结论:移植组NSS评分明显低于对照组与生理盐水组(P<0.05)。在受损伤脑组织周围可发现经Brdu标记的脂肪间充质干细胞。移植组大鼠受损脑组织中胶质纤维酸性蛋白和神经元特异性烯醇化酶阳性表达率明显低于对照组与生理盐水组(P<0.05),且下降速度较快;巢蛋白表达明显高于对照组与生理盐水组(P<0.05)。证实脂肪间充质干细胞通过血脑屏障进入受损大鼠脑组织后,以上调巢蛋白基因的表达来发挥保护神经元、促进神经发育与再生的功能。BACKGROUND：Animal experiments and clinical researches have confirmed that stem cells have a therapeutic effect on the traumatic brain injury.OBJECTIVE：To explore the behaviors of rats of acute traumatic brain injury and expressions of glial fibrillary acidic protein（GFAP）,neuronspecific enolase（NSE）,and nidogen in brain tissue for the treatment of adipose-derived stem cells（ADSCs） transplantation.METHODS：Brain injury model of SD rats were established by free-fall impact method of epidural,and were randomly divided into 3 groups：control group,transplantation group,and saline group.Brdu-labled ADSCs underwent caudal vein injection at 48 hours brain injury in transplantation group;any treatment was not given for the control group;saline underwent caudal vein injection at 48 hours brain injury in saline group.Nerological severiyt score（NSS） method was applied to evaluate the recovery of neurological function in rats.Migration of ADSCs in brain injury tissue was observed by inverted microscope.The expressions of GFAP,NSE,and nidogen in damaged brain tissue of rats were detected by using of immunohistochemistry method.RESULTS AND CONCLUSION：NSS score in transplantation was significantly higher than that in control and saline groups（P0.05）.Brdu-labled ADSCs could be found in damaged brain tissue.The expression of GFAP and NSE in transplantation group was significantly lower than that in control and saline groups in damaged brain tissue of rats（P0.05）,and the rate of decay was rapid.The expression of nidogen in transplantation was significantly higher than that in control and saline groups（P0.05）.It was confirmed that ADSCs through the blood-brain barrier into the damaged brain tissue to protect neuron,and promote the function of neural development and regeneration in terms of up-regulation of nidogen gene expression.

关 键 词：脂肪间充质干细胞 创伤性脑损伤 尾静脉 细胞移植 NSS评分 胶质纤维酸性蛋白 神经元特异性烯醇化酶 巢蛋白 

分 类 号：R394.2[医药卫生—医学遗传学]