目的: 探讨蒙古黄芪多糖对注意缺陷多动障碍(attention deficit and hyperactivity disorder,ADHD)模型大鼠(SHR大鼠)前额叶神经元及脑源性神经营养因子/酪氨酸激酶受体B/环磷腺苷效应元件结合蛋白(BDNF/TrkB/CREB)信号通路作用的影响。方法: 4周龄SHR大鼠20只,分为模型组、蒙古黄芪多糖组(多糖组)、静灵口服液组(静灵组)、哌甲酯组,Wistar大鼠5只设为对照组。灌胃4周后,进行水迷宫实验、旷场实验;麻醉后腹主动脉取血,ELISA法检测血清三磷酸肌醇(IP3)、FosB、c-Fos;结果: 水迷宫实验中各组大鼠行为差异无统计学意义(P＞0.05),多糖组、哌甲酯组、静灵组较模型组站立次数减少(P＜0.05),多糖组、静灵组较模型组理毛次数减少(P＜0.05)。模型组较其他四组神经元结构不完整,核膜碎裂明显且受损严重。多糖组、哌甲酯组较模型组IP3降低(P＜0.05);多糖组、哌甲酯组、静灵组较模型组c-Fos降低(P＜0.05);各组FosB差异无统计学意义(P＞0.05)。多糖组、静灵组BDNF mRNA表达水平较模型组增加(P＜0.05),哌甲酯组、静灵组CREB mRNA表达水平较模型组增加(P＜0.05)。结论: SHR大鼠在旷场实验中的行为改变,可能与蒙古黄芪多糖调节SHR大鼠前额叶中BDNF mRNA的表达,降低IP3、c-Fos水平以及减少前额叶神经元凋亡有关。
Objective: To investigate the effects of Astragalus mongholicus polysaccharides on apoptosis of prefrontal neurons and BDNF / TrkB / CREB signaling pathway in ADHD model rats (SHR). Method: Twenty 4-week old SHR rats were divided into model group, Mongolian astragalus polysaccharide group (polysaccharide group), Jingling oral liquid group (Jingling group), methylphenidate group, and five Wistar rats were set as control group. After four weeks of gavage, water maze test and open field test were performed, and the animals were killed.Blood was taken from abdominal aorta after anesthesia, and determination of Inositol Triphosphate (IP3), FosB and c-Fos in serum by ELISA.After execution, the prefrontal lobe was taken for Nissl staining and Real Time PCR to detect BDNF, TrkB, CREB mRNA in the prefrontal lobe. Results: In the water maze test, there was no significant difference in the behavior of rats in each group (P＞0.05). The standing times of polysaccharide group, methylphenidate group and Jingling group were reduced compared with the model group (P＜0.05), and the hair dressing times of polysaccharide group and Jingling group were reduced compared with the model group (P＜0.05). Compared with the other four groups, the structure of neurons in the model group was incomplete, and the nuclear membrane was obviously fragmented and severely damaged.IP3 in polysaccharide group and methylphenidate group was lower than that in model group (P＜0.05).Compared with model group, c-Fos in polysaccharide group, methylphenidate group and Jingling group decreased (P＜0.05).There was no significant difference in FosB among groups (P＞0.05).The expression level of BDNF mRNA in polysaccharide group and Jingling group was higher than that in model group (P＜0.05), while that of CREB mRNA in methylphenidate group and Jingling group was higher than that in model group (P＜0.05). Conclusion: The behavioral changes of SHR rats in the open field experiment may be related to the regulation of the expression of BDNF mRNA in the prefrontal lobe of SHR rats by astragalus mongholicus polysaccharides, the reduction of IP3, c-Fos levels and the reduction of the apoptosis of prefrontal neurons.
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