孤独症鼠模型海马区脑源性神经营养因子-酪氨酸激酶受体B通路的动态变化研究

关键词：孤独症  脑源性神经营养因子  酪氨酸激酶受体B  海马

Keywords:autism  brain derived neurotrophic factor  TrkB  the hippocampus

摘要：

      摘要 目的：探究孤独症模型鼠海马区脑源性神经营养因子（brain derived neurotrophic factor，BDNF）-酪氨酸激酶受体B（tyrosine kinase receptor B，TrkB）通路在不同时间点的动态表达情况，为孤独症发病机制和临床治疗的研究提供思路。 方法：随机选取孕12.5天Wistar雌鼠24只，实验组12只腹腔注射丙戊酸钠，对照组12只腹腔注射生理盐水。分别对两组雌鼠生产的仔鼠进行行为学检测。于仔鼠P7、P21、P28、P35、P42时，从实验组和对照组中随机各取8只，采用Western Blot对两组仔鼠海马区BDNF和TrkB蛋白表达进行检测，采用Rt-PCR对两组仔鼠海马区BDNF和TrkB的mRNA表达进行检测。 结果：与对照组仔鼠相比，实验组仔鼠存在以下异常：①行为学方面：社会交流能力下降，重复性刻板行为增加，学习记忆能力下降，以上差异均有显著性意义（P＜0.05）。②Western Blot检测：在P7、P21、P28时，实验组仔鼠海马区BDNF和TrkB蛋白表达都高于对照组（P<0.05），而在P35、P42时，实验组仔鼠海马区BDNF和TrkB蛋白表达低于对照组（P<0.05）。③Rt-PCR检测：在P7、P21、P28时，实验组仔鼠海马区BDNF和TrkB的mRNA表达都高于对照组（P<0.05），而在P35、P42时，实验组仔鼠海马区BDNF和TrkB的mRNA表达低于对照组（P<0.05）。 结论：孤独症模型鼠海马区BDNF-TrkB通路早期过度表达，后期表达下降，且此改变在转录水平就已发生。

Abstract:

      Abstract Objective： To provide ideas for the study of the pathogenesis of autism spectrum disorders by exploring the dynamic expression of BDNF-TrkB pathway in hippocampus of autism model rats at different time points. Method： Twenty-four female Wistar rats on day 12.5 of pregnancy were randomly selected. 12 rats in the experimental group were intraperitoneally injected with VPA and 12 rats in the control group were intraperitoneally injected with normal saline. The behavior of the offspring of the two groups were detected. At the time of P7， p21， P28， p35 and p42. The expression of BDNF and TrkB protein was detected by Western Blot and the mRNA expression of BDNF and TrkB was detected by RT-PCR. Result： When compared with the offspring of the control group，the following abnormalities were found in the offspring of the model group：①Behavior： social communication ability and learning and memory ability decreased，while repetitive stereotyped behavior increased. The above differences were statistically significant (P<0.05). ②Western Blot analysis： at P7， p21， P28， the expression of BDNF and TrkB protein in hippocampus of model group was higher than that of the control group (P<0.05)，while at p35 and p42，the expression of BDNF and TrkB protein in hippocampus of the model group was lower than that of the control group(P<0.05). ③RT-PCR detection： at P7， p21， P28， the mRNA expression of BDNF and TrkB in hippocampus of the model group was higher than that of the control group (P<0.05)， but at p35 and p42，the mRNA expression of BDNF and TrkB in hippocampus of the model group was lower than that of the control group(P<0.05). Conclusion： The expression of BDNF TrkB pathway in hippocampus of autism model rats is over expressed in the early stage and decreased in the later stage， and this change has appeared at the transcriptional level.