目的 研究高脂膳食诱导的母体肥胖和肥胖抵抗对胎鼠神经干细胞增殖和分化的影响。方法 将16只雌性Sprague-Dawley大鼠随机用对照或高脂膳食喂养8 w后,分为对照(control-control, CC)、肥胖易感(obesity-prone, OP)和肥胖抵抗(obesity-resistant, OR)3组,每组4只,与同周龄雄性Sprague-Dawley大鼠交配成功后,收集孕17.5 d (gestational day 17.5, GD17.5) 和GD19.5胎鼠,每组4只。测定胎鼠的体重和体长,Western blot分析脑组织Nestin、DCX (doublecortin)、NeuN (neuronal nuclei)、GFAP(glial fibrillary acidic protein)及CREB-BDNF(cAMP-response element binding protein, brain-derived neurotrophic factor)信号通路蛋白的表达。结果 在GD17.5,与CC组胎鼠相比,OP组胎鼠体重增加(P<0.05),脑组织Nestin、CREB蛋白、p-CREB/CREB比值的表达量显著下降(P<0.01, P<0.01, P<0.01）;OR组胎鼠体重、体长增加(P<0.01, P<0.01), 脑组织Nestin、GFAP、CREB蛋白的表达量显著下降(P<0.05, P<0.01, P<0.01)。与OR组胎鼠相比,OP组胎鼠体长减少(P<0.01),脑组织Nestin蛋白、p-CREB/CREB比值的表达量显著下降,GFAP蛋白的表达量显著上升(P<0.01, P<0.05, P<0.01)。在GD19.5,与CC组胎鼠相比,OP组胎鼠体重增加(P<0.05),脑组织Nestin、DCX、GFAP蛋白的表达量下降(P<0.01, P<0.05, P<0.01);OR组胎鼠胎鼠体重、体长增加(P<0.01, P<0.01),脑组织Nestin、DCX蛋白的表达量下降,CREB 蛋白、p-CREB/CREB比值上升(P<0.01, P<0.01, P<0.01, P<0.01)。与OR组胎鼠相比,OP组胎鼠体长减少(P<0.01),脑组织GFAP、CREB、BDNF蛋白的表达量、p-CREB/CREB比值下降(P<0.05, P<0.01, P<0.05, P<0.01)。结论 高脂膳食诱导的母体肥胖和肥胖抵抗可以抑制胎鼠神经干细胞的增殖和分化,神经干细胞、祖细胞以及星形胶质细胞的数量减少。
Abstract
Objective To investigate the effects of maternal obesity and obesity resistance induced by high-fat diet on proliferation and differentiation of neural stem cells in fetal rats. Methods A total of 16 female Sprague-Dawley rats were randomly fed the control or high-fat diet for 8 weeks and then divided into three groups: control-control (CC), obesity-prone (OP) and obesity-resistant (OR), with 4 rats in each group. After mating with male rats of the same week, gestational day 17.5(GD17.5) and GD19.5 fetal rats were collected with, 4 rats in each group. The body weight and length of fetal rats were measured. The expressions of Nestin, DCX (doublecortin), NeuN (neuronal nuclei), GFAP (glial fibrillary acidic protein) and CREB-BDNF (cAMP-response element binding protein, brain-derived neurotrophic factor) signaling pathway proteins in brain tissue were analyzed by Western Blot. Results On GD17.5, compared with the CC group, body weight was increased (P<0.05), and the expressions of Nestin, CREB protein, P-CREB /CREB ratio significantly decreased in OP group (P<0.01, P<0.01, P<0.01). In the OR group, body weight and length were increased (P<0.01, P<0.01), and the expressions of Nestin, GFAP and CREB proteins significantly decreased (P<0.05, P<0.01, P<0.01). Compared with the OR group, body length was decreased (P<0.01), and the expression of Nestin protein and p-CREB/CREB ratio decreased significantly in brain tissue, while the expression of GFAP protein increased significantly in OP group (P<0.01, P<0.05, P<0.01). On GD19.5, compared with the CC group, body weight was increased (P<0.05), and the expressions of Nestin, DCX and GFAP significantly decreased in the OP group (P<0.01, P<0.05, P<0.01).In the OR group, body weight and length were increased (P<0.01, P<0.01), and the expressions of Nestin and DCX proteins decreased, while the CREB protein and p-CREB/CREB ratio significantly increased (P<0.01, P<0.01, P<0.01, P<0.01). Compared with the OR group, body length was decreased (P<0.01), and the expressions of GFAP, CREB, BDNF protein, p-CREB/CREB ratio in brain tissue significantly decreased in the OP group (P<0.05, P<0.01, P<0.05, P<0.01). Conclusion Maternal obesity and obesity resistance induced by high-fat diet can inhibit the proliferation and differentiation of neural stem cells in fetal rats, and the numbers of neural stem cells, neural progenitor cell and astrocytes reduced.
关键词
高脂膳食 /
大鼠 /
孕期 /
肥胖 /
肥胖抵抗 /
神经发生
Key words
high-fat diet /
rat /
pregnancy /
obesity /
obesity resistant /
neurodevelopment
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基金
国家自然科学基金（No. 81273070）
