移植活化小胶质细胞改善急性脑梗死小鼠神经功能的作用机制  

Activated microglia transplantation improves the neural function following acute cerebral infarction in mice

作　　者：项薇[1,2] 潘速跃[1] 谭焱[2] 武肖娜[2] 张洧 邓镇[1] 田灿辉[1] Xiang Wei Pan Su-yue Tan Yan Wu Xiao-na Zhang Wei Deng Zhen Tian Can-hui(Department of Neurology Nanfang Hospital, Nanfang Medical University, Guangzhou 510515, Guangdong Province, China Department of Neurology, General Hospital of Guangzhou Military Command of PLA, Guangzhou 510010, Guangdong Province, China)

机构地区：[1]南方医科大学附属南方医院神经内科,广东省广东市510515 [2]解放军广州军区广州总医院神经内科,广东省广东市510010

出　　处：《中国组织工程研究》2017年第16期2552-2557,共6页Chinese Journal of Tissue Engineering Research

基　　金：广东省医学科学技术研究基金项目(A2016067);课题名称:let7i 在 rt-PA 溶栓后脑水肿及出血转化中的作用及机制研究;广东省自然科学基金项目(2014A030313598);课题名称:阿托伐他汀钙对钙化性主动脉瓣狭窄作用机制的实验研究~~

摘　　要：背景:静止状态的小胶质细胞担负免疫监视的重任,而对活化后小胶质细胞的作用则存在较大争议。目的:分析活化小胶质细胞在急性脑梗死中的作用机制。方法:选取96只雄性昆明小鼠,随机分为4组。其中移植组、安慰剂组及空白对照组小鼠经线栓栓塞大脑中动脉法建立永久性局灶性脑梗死动物模型,移植组建模后12 h经锁骨下静脉注入小胶质细胞悬液,安慰剂组注入同体积小胶质细胞培养基;空白对照组仅建模;假手术组小鼠经假手术12 h后注入同移植组同体积的小胶质细胞悬液。观察建模后12,24,72 h时神经功能Zea-longa评分、脑源性神经营养因子表达情况及72 h时脑梗死体积、存活神经细胞(即微管相关蛋白2阳性率)差异。结果与结论:(1)假手术组小鼠各时段Zea-longa评分均为0分,显著低于其他3组小鼠(P<0.01);小胶质细胞移植24,72 h时,移植组Zea-longa评分显著低于安慰剂组和空白对照组小鼠(P<0.01);(2)移植组各时段脑组织脑源性神经营养因子阳性表达率均显著高于其他3组小鼠(P<0.01);(3)假手术组未见脑梗死,小胶质细胞移植72 h时,移植组小鼠脑梗死体积为显著低于安慰剂组和空白对照组(P<0.01),微管相关蛋白2阳性率显著高于安慰剂组和空白对照组(P<0.01);(4)结果表明,活化小胶质细胞对提高神经细胞存活率、促进脑神经功能恢复、抑制脑梗死体积扩大等具有积极影响。BACKGROUND： Microglia play an important role in immune surveillance in their quiescent state, but the role of the activated microglia is under discussion. OBJECTIVE： To analyze the mechanism of activated microglia in acute cerebral infarction. METHODS： Totally 96 male Kunming mice were selected and randomly divided into four groups, including transplantation, placebo, blank control and sham operation groups. Permanent occlusion of the middle cerebral artery was performed using suture method in the mice of the transplantation, placebo and blank control groups, followed by injection of microglia suspension via subclavian vein, medium containing the same volume of microglia, and nothing, respectively, at 12 hours after modeling. In the meanwhile, the same amount of microglia suspension was injected into the mice of the sham operation group. The Zea-longa scale and brain-derived neurotrophic factor expression at 12, 24 and 72 hours after modeling, the volume of cerebral infarction and the number of nerve cells positive for microtubule-associated protein-2 at 72 hours after modeling were detected. RESULTS AND CONCLUSION： The Zea-longa scale score was 0 point in the sham operation group, which was significantly lower than that in the other three groups at each time point after modeling （P 〈 0.01）. The Zea-longa scores in the transplantation group were significantly lower than those in the placebo and blank control groups at 24 and 72 hours after transplantation （P 〈 0.01）. The positive expression rate of brain-derived neurotrophic factor in the transplantation group was significantly higher than that in the other three groups after transplantation （P 〈 0.01）. The sham group showed no infarction, while the size of cerebral infarction in the transplantation group was significantly lower than that in the placebo and blank control groups （P 〈 0.01）, and the microtubule-associated protein-2 positive rate was significantly higher than that in the placebo and blank control groups （P 〈 0.01�

关 键 词：胶质细胞 脑梗塞 脑源性神经营养因子 组织工程 组织构建 活化小胶质细胞 急性脑梗死 作用机制 广东省自然科学基金 

分 类 号：R318[医药卫生—生物医学工程]