孕期和哺乳期n-3多不饱和脂肪酸对子代小鼠成年脑神经发生及凋亡的影响  

Dietary n-3 polyunsaturated fatty acids during maternal pregnancy and lactation affect the neurogenesis and apoptosis in adult brain of the mouse offsprings

作　　者：付慧聪 高亚兵[2] 樊超男[1] 颜克松[3] 路媛媛[1] 卢燕飞[1] 彭瑞云[2] 齐可民[1] 

机构地区：[1]首都医科大学附属北京儿童医院北京市儿科研究所营养研究室,北京100045 [2]军事医学科学院放射与辐射研究所,北京100850 [3]中国人民解放军总医院附属304医院实验动物中心,北京100037

出　　处：《中国体视学与图像分析》2015年第2期161-169,共9页Chinese Journal of Stereology and Image Analysis

基　　金：国自然青年基金(81100630);北京市科技新星项目(XX2012047)

摘　　要：目的探讨生命早期n-3多不饱和脂肪酸(n-3 polyunsaturated fatty acids,n-3 PUFAs)营养状态对成年期脑神经元发生及凋亡的影响。方法使用20只3-4 w龄清洁级C57BL/6J雌性小鼠,随机分为两组(10只/组),分别给予n-3 PUFAs缺乏和n-3 PUFAs饲料喂养;12-14 w龄时与雄性小鼠合笼交配繁殖。仔鼠生后21 d断乳时,随机挑选20只n-3 PUFAs缺乏组仔鼠用n-3 PUFAs饲料喂养,挑选等量n-3 PUFAs饲料组仔鼠用n-3 PUFAs缺乏饲料喂养,剩余仔鼠用与母鼠相同饲料继续喂养,至仔鼠3月龄时结束实验。小鼠麻醉处死后取全脑组织,采用脂肪酸甲酯化-气相色谱分析对脑脂肪酸进行测定;采用免疫组织化学技术对海马CA3区B淋巴细胞瘤-2蛋白(B-cell lymphoma-2,Bcl-2)、Bcl-2相关X蛋白(Bcl-2 associated X protein,Bax)和钙视网膜结合蛋白(Calretinin,CR)表达进行分析。结果与n-3 PUFAs缺乏饲料持续喂养的仔鼠相比,孕期和哺乳期n-3 PUFAs缺乏而断乳后给予n-3 PUFAs饲料喂养的仔鼠,成年后脑组织n-3 PUFAs含量明显升高(P<0.05),但Bcl-2、Bax和CR的表达量均未发生显著性变化,仍然低于n-3 PUFAs饲料持续喂养仔鼠的水平。孕期和哺乳期n-3 PUFAs饲料喂养而断乳后给予n-3 PUFAs缺乏饲料喂养的仔鼠,成年后脑组织n-3PUFAs含量较n-3 PUFAs饲料持续喂养的仔鼠明显降低(P<0.05);Bcl-2和CR的表达量高于n-3 PUFAs缺乏饲料持续喂养的仔鼠(P<0.05)。结论孕期和哺乳期保证适量n-3 PUFAs的摄入,有助于成年期脑神经元的发生,并减少神经元凋亡。Objective To investigate the effects of dietary n- 3 polyunsaturated fatty acids（ n- 3PUFAs） during maternal pregnancy and lactation on the neurogenesis and apoptosis in adult brain of the mouse offsprings. Methods Twenty 3- 4 week-old C57 BL /6J female mice were randomly divided into 2groups,and were fed with two types of diets： the n- 3 PUFAs deficient diet and n- 3 PUFA containing diet,respectively. After 8-weeks feeding,the mice were mated with male mice for breeding pups. At postnatal day 21,twenty pups from each of the n- 3 PUFA deficient diet and n- 3 PUFA diet groups were selected,and then fed with the n- 3 PUFA diet and n- 3 PUFA deficient diet,respectively. The rest of the pups were fed with the same diets as their mothers. At 3 months of age,the offspring mice were sacrificed and brain samples were collected. Fatty acids in the brain tissue were analyzed by gas chromatography and expressed as percent（ %） of the total fatty acids. Expressions of the B- cell lymphoma- 2（ Bcl- 2）,Bcl- 2 associated X protein（ Bax） and calretinin（ CR） in the hippocampus were determined by immunohistochemistry. Results Feeding with the n- 3 PUFA containing diet to pups from the n- 3deficient diet group significantly increased the n- 3 PUFA concentration,but did not change the expressions of Bcl- 2,Bax and CR in the hippocampus,which were significantly lower compared with that in the mice fed with n- 3 PUFA diet continuingly（ P〈0. 05）. Feeding with n- 3 PUFA deficient diet to pups from the n- 3 PUFA diet group significantly reduced the n- 3 PUFA concentration,but did not reduce the expressions of Bcl- 2 and CR significantly（ P〈0. 05）. Conclusions Appropriate intake of n- 3 PUFA during maternal pregnancy and lactation is beneficial for offspring brain neurogenesis and reducing apoptosis in neurons.

关 键 词：N-3多不饱和脂肪酸 生命早期 海马 神经发生 凋亡 

分 类 号：R153.1[医药卫生—营养与食品卫生学]