IGF-1对不同年龄缺血性脑损伤大鼠神经发生的影响(英文)  

Effects of IGF-1 on Neurogenesis after Focal Cerebral Ischemia In Young and Older Rats

作　　者：王琳娜[1] 崔景彬[2] 杨华山[3] 

机构地区：[1]中南大学湘雅医院,湖南长沙410008 [2]郑州大学医学院,河南郑州450052 [3]郑州大学护理医学院,河南郑州450052

出　　处：《现代生物医学进展》2008年第5期805-809,F0002,共6页Progress in Modern Biomedicine

基　　金：Tackle key problems in science technology in Henan province(324410034)

摘　　要：目的:检测胰岛素样生长因子-1(IGF-1)对青年和老年大鼠局灶脑缺血后神经发生及其后细胞生存的影响。方法:健康雄性SD青年鼠(3-4个月)和老年鼠(1年)随机分组,侧脑室注入IGF-1,1天后进行大鼠大脑中动脉阻塞(MCAO),对照组由生理盐水取代。采用BrdU标记方法鉴定MCAO后7d和28d的增殖细胞。BrdU于MCAO后第6d由腹腔注入。免疫组化法检测7天后Brdu、PSA-NCAM标记细胞和28天后BrdU、BrdU/MAP2双标细胞。结果:老年组中BrdU阳性细胞的数目7d后较对照组增加5.1倍;青年组中Brdu阳性细胞的数目7d后较对照组增加5.5倍。28d后,BrdU阳性细胞的残留率在青年IGF-1处理组和老年IGF-1处理组中分别是79.2%和75.1%,分别相对于对照组的77.1%和52.3%。老年组中PSA-NCAM阳性细胞的数目7d后较对照组增加3.2倍:青年组中PSA-NCAM阳性细胞的数目7d后较对照组增加3.7倍。28d后,BrdU/MAP2阳性细胞在青年IGF-1处理组较对照组增加7.0倍,在老年IGF-1处理组较对照组增加4.9倍。结论:此结果提示局部应用IGF-1进行缺血前预处理,在青年鼠和老年鼠中均能诱导神经发生,且在老年鼠中能明显提高神经发生后的增殖细胞的生存率和向神经元分化的能力。这一研究结果将有助于研究IGF-1在中老年脑损伤病人中的治疗性应用。Objective： In order to examine the effect of IGF-1 on neurogenesis after focal cerebral ischemia in young and older rats. IGF-1 was applied by transventricular injection one day before operation of permanent middle cerebral artery occlusion（ MCAO ）. In contrast, the control groups were treated with vehicle. Methods： Bromodeoxyuridin （BrdU）was used as a marker of the proliferating cells, and PSA-NCAM as a marker of neural precursor cells, BrdU-labeled cells immunoreacted with MAP2 as a marker of differentiated neural precursor cells 28d after MCAO. Rats were administered with BrdU 6 days after MCAO. Immunohistochemistry was used to detect the expression of BrdU and PSA-NCAM immunoreactivity in cortex and hippocampus 7 days and 28 days after MCAO, double immunohistochemistry was used to detect the expression of MAP2 of BrdU-labeled cells 28d after MCAO. Results： The number of BrdU-labeled cells and PSA-NCAM positive cells increased 5.1 fold and 3.2 7d after IGF-1 infusion in older rats, and 5.5 fold and 3.2 fold in young rats, compared with vehicle-treated group（p〉0.05 ）. The residual rate of BrdU-labeled cells were 79.2% and 75.1% respectively in young and older rats （p〉0.05）, in contrary to 77.1% and 52.3% （p〈0.05）in vehicle-treated groups 28d after MCAO. BrdU/MAP2 positive cells increased after IGF-1 infusion with more clear effect in young group （p〈0.05）, compared with vehicle-treated group. Conclusion： Our results indicated that IGF-1 pretreatment induced the neurogenesis, ameliorated the survival of post-proliferation cells in MCAO rats and induced neural precursor cells to differentiate into neuron. Our finding will be helpful to developing therapeutic application ofIGF-1 after brain injury in older patients.

关 键 词：衰老 局灶脑缺血 IGF-1 神经发生 神经干细胞 大鼠 

分 类 号：R743.22[医药卫生—神经病学与精神病学]