粒细胞集落刺激因子诱导淀粉样前体蛋白转基因小鼠神经再生及对认知功能的改善  

Granulocyte colony-stimulating factor induces neurogenesis and improves cognition in amyloid precursor protein transgenic mouse model of Alzheimer＇s disease

作　　者：朱正禹[1] 王萍[1] 郭雨霁[1] 谢兆宏[1] 来超[1] 毕建忠[1] 

机构地区：[1]山东大学第二医院神经内科,济南250033

出　　处：《中华老年医学杂志》2012年第9期819-822,共4页Chinese Journal of Geriatrics

基　　金：基金项目：国家自然科学基金资助项目（30670745）

摘　　要：目的探讨粒细胞集落刺激因子（G—CSF）对淀粉样前体蛋白（APP）转基因小鼠认知功能的改善及对神经再生的影响。方法选用36只APP转基因小鼠作为AD动物模型，随机分为G-CSF治疗组和对照组各18只。治疗组皮下注射G—CSF，对照组给予等体积磷酸盐缓冲液（PBS）皮下注射。给药后第7d、14d、28d进行Morris水迷宫测试，计算其逃避潜伏期。水迷宫测试后取外周血，利用流式细胞术观察G-CSF对骨髓造血干细胞的诱导作用。免疫组化及免疫荧光双标观察脑内神经元再生。结果与对照组比较，治疗组小鼠在第7d、14d、28d的逃避潜伏期分别为（27．19±4．07）S、（26．48±5．29）s、（24．97±3．61）S，较对照组明显缩短（P值分别为0．000、0．010、0．002）；治疗组小鼠外周血CD34＋／CD45＋双阳性细胞百分率在第7d、14d、28d分别为0．358±0．161、0．223±0．038、0．168±0．049，较对照组明显增加（P值分别为0．007、0．000、0．003），脑内检测到CD34＋阳性细胞，海马齿状回、皮质均可见BrdU＋阳性细胞，同时可检测到BrdU＋／Nestin＋和Brdu＋／MAP-2＋双阳性细胞。结论G-CSF皮下注射可明显改善APP转基因小鼠的认知功能，可能与动员外周骨髓造血干细胞增殖、分化，并向脑内定向迁移有关。Objective To investigate the effect of granulocyte colony-stimulating factor（G-CSF） and its effect on the cognation in the PDGF hAPPV717I transgenic mice of Alzheimer＇s disease model. Methods Totally 36 PDGF hAPPV717I transgenic mice were randomly divided into two groups： G- CSF group and control group. The G-CSF group was subcutaneously injected with 50 ug . kg-1 . d-1 of G--CSF for 7 days. The control group was injected subcutaneously with an equal volume of PBS in parallel. The animals were tested in Morris water maze on the 7th, 14th, and 28th days after the last day of the injection, and the escape latency was recorded. Once the test was completed, the peripheral blood was taken to evaluate the effect of G-CSF to induce hematopoietic stem cells （HSCs） via flow cytometry. Then the mice were killed, their brains were quickly removed and frozen on dry ice. With the immunohistochemical staining and double immunofluorescence staining, the neurogenesis could be observed in the model mice. Results We found that G-CSF significantly shortened the escape latencies in PDGF-hAPPV717I transgenic mice compared to controls on the 7th, 14th, and 28th day after G-CSF treatment [7 d： （27.19±4.07） s and （46.07±7.21） s , P〈0.000; 14 d： （26.48± 5.29） sand （42.99±11.70） s , P〈0.010; 28 d： （24.97±3.61） s and （45.54±9.55） s, P〈 0. 002）]. At the same time, we found that the percentage of CD34＋/CD45＋ cells in the peripheral blood was 0. 358±0. 161, 0. 223±0. 038, 0. 168±0. 049 on the 7th, 14th, and 28th day after G-CSF treatment, respectively. Compared with the control group （0.073±0.026, 0.067±0.034, 0.0724± 0. 037）, the percentage of CD34＋/CD45＋ cells in the peripheral blood were increased （P〈0. 001）. BrdU＋ cells were found in dentate gyrus （DG） of hippocampus and the cortex of the G-CSF group,where the BrdU＋ /Nestin＋ and BrdU＋/MAP 2＋ cells were also detected positively. Conclusions Subcutaneous administration of G-CSF may improve the cog

关 键 词：APP转基因小鼠 粒细胞集落刺激因子 水迷宫 神经元再生 认知功能 

分 类 号：R749.16[医药卫生—神经病学与精神病学]