【摘 要】
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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
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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、14 d、28 d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CD 34+/CD 45双阳性细胞百分率在第7d、14 d、28 d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.
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