星形胶质细胞特异性敲除Adam10基因对周细胞和血脑屏障的影响  

Effects of Knockout Astrocytic Adam10 Gene on Pericytes and Blood Brain Barrier

作　　者：熊颖[1] 张强 潘邓记[2] XIONG Ying;ZHANG Qiang;PAN Deng-ji(Department of Radiology, Huazhong University of Science and Technology,Wuhan 430030, China;Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology,Wuhan 430030, China)

机构地区：[1]华中科技大学同济医学院附属同济医院放射科,武汉430030 [2]华中科技大学同济医学院附属同济医院神经内科,武汉430030

出　　处：《神经损伤与功能重建》2019年第3期109-112,共4页Neural Injury and Functional Reconstruction

基　　金：国家自然科学基金(No.81471230;No.81601480;No.81571206)

摘　　要：目的:探讨Adam10基因对于星形胶质细胞与周细胞之间信号交流及对血脑屏障(BBB)完整性的影响。方法:利用Cre-loxp技术得到星形胶质细胞特异性敲除Adam10基因小鼠(Gfap^(cre)-Adam10^(lox/lox))纳入敲除组,将同胎基因型为Adam10^(lox/lox)的小鼠纳入对照组。免疫荧光双标技术检测周细胞心肌素(myocardin)蛋白和平滑肌肌动蛋白(SMA)的表达;电镜分析周细胞的变性和凋亡、基底膜和BBB的破坏;激光散斑衬比成像技术观察脑组织局部血流灌注的改变。结果:特异性敲除星形胶质细胞Adam10基因后,可影响相邻的星形胶质细胞和周细胞之间的信号交流,导致周细胞表达myocardin蛋白和SMA蛋白减少;敲除组呈现出更为明显的周细胞变性、凋亡和BBB破坏;进而影响血管密度和血流速度。结论:Adam10基因可能影响星形胶质细胞与周细胞之间的信号交流,并可能因此而影响BBB完整性和脑组织的血流灌注。Objective: To investigate the effect of Adam10 gene on the cross-talk between astrocyte and pericyte, and on the integrity of blood-brain barrier (BBB). Methods: Adam10 gene knockout mice (Gfapcre-Adam10lox/ lox) were obtained by Cre-loxp technique. Adam10lox/lox mice were used as control. The expression of myocardin and smooth muscular actin (SMA) protein in pericytes was detected by double immunofluorescence labeling technique. The degeneration and apoptosis of pericytes, destruction of basement membrane and BBB were analyzed by electron microscopy. Laser speckle imaging was used to observe the changes of regional cerebral blood perfusion. Results: Specific knockout ofAdam10 gene in astrocytes affectted the signal exchange between astrocyte and pericyte;decreased the myocardin and SMA protein expression in pericytes;induced pericyte degeneration and apoptosis;damaged BBB;and affected vascular density and blood flow velocity in brain cortex. Conclu. sion: Adam10 gene may affect the signal exchange between astrocytes and pericytes, thus affecting the integrity of BBB and cerebral blood perfusion.

关 键 词：星形胶质细胞 周细胞 ADAM10 血脑屏障 激光散斑衬比成像 

分 类 号：R741[医药卫生—神经病学与精神病学] R741.02[医药卫生—临床医学]