CAJ | 학술논문

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.
목적 탐토립세포집락자격인자(G-CSF)대정분양전체단백(APP)전기인소서인지공능적개선급대신경재생적영향. 방법 선용36지APP전기인소서작위AD동물모형,수궤분위G-CSF치료조화대조조각18지.치료조피하주사G-CSF,대조조급여등체적린산염완충액(PBS)피하주사.급약후제7d、14d、28d진행Morris수미궁측시,계산기도피잠복기.수미궁측시후취외주혈,이용류식세포술관찰G-CSF대골수조혈간세포적유도작용.면역조화급면역형광쌍표관찰뇌내신경원재생. 결과 여대조조비교,치료조소서재제7d、14 d、28 d적도피잠복기분별위(27.19±4.07)s、(26.48±5.29)s、(24.97±3.61)s,교대조조명현축단(P치분별위0.000、0.010、0.002);치료조소서외주혈CD 34+/CD 45쌍양성세포백분솔재제7d、14 d、28 d분별위0.358±0.161、0.223±0.038、0.168±0.049,교대조조명현증가(P치분별위0.007、0.000、0.003),뇌내검측도CD34′양성세포,해마치상회、피질균가견BrdU+양성세포,동시가검측도BrdU+/Nestin+화BrdU-/MAP-2+쌍양성세포. 결론 G-CSF피하주사가명현개선APP전기인소서적인지공능,가능여동원외주골수조혈간세포증식、분화,병향뇌내정향천이유관.
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 μg · 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±0.034,0.072± 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+ /Ncstin- and BrdU-/MAP-2+ cells were also detected positively.Conclusions Subcutaneous administration of G- CSF may improve the cognition in APP transgenic mouse model of AD.G-CSF may mediate the proliferation,differentiation of hcmatopoietic stem cells (HSCs).and may induce the neural stem cells into the brain.