脑源性神经营养因子通路的抑制介导孕期摄食限制所致的雄性子代大鼠海马发育损伤

发布时间：2018-02-27 23:28

  本文关键词： 孕期摄食限制 海马 宫内编程 脑源性神经营养因子 突触可塑性　出处：《中国药理学与毒理学杂志》2015年03期 　论文类型：期刊论文

【摘要】：目的观察孕期摄食限制(PFR)所致雄性子代鼠海马结构及功能损伤改变,并探讨其发生机制。方法健康Wistar雌性大鼠受孕后第11~20天(GD11~GD20)限食,给予正常对照组日均摄食量的50%,部分孕鼠于GD20麻醉处死取胎鼠;其余孕鼠自然生产所得雄性子代鼠断奶后给予高脂饮食喂养,一批于生后17周龄(PW17)麻醉处死,另一批从PW17起,21 d内给予慢性不可预知性刺激(UCS)后,于PW20处死,取海马组织。采用HE染色和(或)透射电镜进行组织学观察,ELISA试剂盒检测胎鼠血皮质酮水平,PCR检测海马糖皮质激素受体(Gr)、脑源性神经营养因子(Bdnf)通路、突触可塑性相关基因的mRNA表达。结果与正常对照组相比,PFR胎鼠海马显示亚细胞水平病理损伤,胎血皮质酮水平增加了1.19倍(P0.05),Gr mRNA表达升高了38%(P0.05),Bdnf、N-甲基-D-天冬氨酸受体亚单位1(Nr1)、Nr2B和突触蛋白Ⅰ的mRNA表达分别降低了25.0%,16.1%,16.1%和17.6%(P0.05)。与高脂对照组相比,PFR成年子代鼠海马仅显示轻微病理改变,而PFR成年子代鼠在UCS后,海马病理损伤明显,表现为锥体细胞层极薄,细胞间隙增大,细胞数目减少和核皱缩,同时海马c AMP应答元件结合蛋白、Bdnf、酪氨酸激酶受体及Nr1 mRNA表达分别显著降低了51.0%,50.0%,52.0%和33.3%(P0.05,P0.01)。结论 PFR可致雄性子代鼠海马结构及功能损伤,其机制可能与PFR所致的母源性高GC引起子代鼠海马Bdnf通路抑制有关。
[Abstract]:Objective to observe the changes of hippocampal structure and function in male offspring induced by dietary restriction during pregnancy, and to explore its mechanism. Methods healthy Wistar female rats were treated with GD11GD20 on the 20th day after conception. Some of the pregnant rats were anesthetized by GD20 to kill the fetuses, while the rest of the pregnant rats were fed with high-fat diet after weaning, and some of them were anesthetized and executed at the age of 17 weeks after birth. Another group received chronic unpredictable stimulation within 21 days from the onset of PW17 and then died in PW20. Using HE staining and / or transmission electron microscope (TEM) to detect serum corticosterone level in fetal rats. The glucocorticoid receptor (Gr) and brain-derived neurotrophic factor (BDNF) pathway in hippocampus were detected by PCR. The expression of synaptic plasticity related gene mRNA. Results compared with the normal control group, the hippocampus of fetal rats showed subcellular pathological damage. Fetal serum corticosterone level increased by 1.19 times P0.05Gr mRNA expression and increased the expression of mRNA of N- methyl-Daspartic acid receptor subunit N- Nr2B and synaptophysin 鈪，

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