孕期乙醇暴露所致的胎鼠海马神经毒性作用及其对神经元结构和相关功能的影响

发布时间：2018-05-19 22:20

  本文选题：乙醇 + 地塞米松　； 参考：《广东医学》2017年10期

【摘要】：目的研究孕期乙醇暴露对胎鼠海马神经元结构与相关功能的影响,并探讨其可能的发生机制。方法将体重为250~300 g的Wistar大鼠,以雌∶雄=2∶1合笼,雌鼠受孕后随机分为对照组、地塞米松组和乙醇组。孕9 d起,地塞米松组以1 mg/(kg·d)地塞米松皮下注射,乙醇组以4 g/(kg·d)乙醇灌胃,对照组给予等体积蒸馏水,连续给药至受孕20 d。孕鼠于受孕20 d经异氟醚麻醉后,剖宫取出胎鼠,选取胎鼠数量在8~14只的母鼠,胎鼠断头取血,并分离胎海马组织,实时定量PCR技术检测海马相关功能的基因表达。各组取胎鼠全脑常规固定、制片,并行病理组织学(HE染色)和细胞超微结构观察。结果 HE染色显示,孕期地塞米松和乙醇暴露的胎鼠海马神经元排列整齐、规则,与对照组比较无明显改变;电镜结果显示,与对照组相比,地塞米松组和乙醇组出现内质网扩张,高尔基体肥大。孕期地塞米松暴露后,雄性胎鼠胰岛素样生长因子(IGF)-1、IGF-1R、AKT2、Bcl-2及Caspase-8、SNAP25、NR2B和GLUR1、11β-HSD-1和MR的mRNA表达显著升高(P0.05,P0.01),Bax、Cdc42、NR1和GLUR2、PKACa、11β-HSD-2和BDNF的mRNA表达显著下降(P0.01),Bax/Bcl-2比值显著降低(P0.01),Cyclin A、Rac、Rho A、NR2A、GLUR3和Syn1、GR、Egr-1及5HTr7表达无显著改变。孕期乙醇暴露后,IGF-1、IGF-1R、AKT2、CDK2、Bcl-2、Caspase-8、Rac、NR1、NR2A、NR2B、Syn1、SNAP25、HCN1和HCN2、GR、MR、5HTr7及Egr-1的mRNA表达显著升高(P0.05,P0.01),Cyclin A、Bax、Caspase 3、Cdc42、GLUR2和GLUR3、PKACa及BDNF的mRNA表达显著降低(P0.01),Bax/Bcl-2比值显著降低(P0.01),Rho A和GLUR1、11β-HSD-1的mRNA表达差异无统计学意义。结论孕期乙醇暴露在一定程度上不仅影响了胎鼠海马神经结构,而且海马神经元增殖与凋亡、学习与记忆、GC代谢与营养发育等相关功能发生了变化,并出现细胞的增殖和代谢升高的趋势,表明海马损伤的同时出现了一定的代偿作用。乙醇所致的胎鼠海马结构和相关功能改变可能与c AMP/Egr-1/GR/BDNF通路改变有关。
[Abstract]:Objective to study the effects of alcohol exposure during pregnancy on the hippocampal neuronal structure and related functions in fetal rats and to explore its possible mechanism. Methods Wistar rats weighing 250g were randomly divided into control group, dexamethasone group and ethanol group with female: male 2: 1 cage. From the 9th day of pregnancy, the dexamethasone group was subcutaneously injected with dexamethasone 1 mg/(kg d, the ethanol group was given 4 g/(kg d) ethanol, and the control group was given the same volume distilled water until 20 days of pregnancy. The pregnant rats were anesthetized by isoflurane on the 20th day of pregnancy. The fetal rats were taken out from the uterus, and the fetal rats with 814 fetal rats were selected. The fetal hippocampus was isolated and the fetal hippocampal tissues were isolated. The expression of genes related to hippocampal function was detected by real-time quantitative PCR technique. Fetal rats in each group were treated with routine brain fixation, radiography, HE staining and ultrastructure observation. Results HE staining showed that the hippocampal neurons of fetal rats exposed to dexamethasone and ethanol during pregnancy were arranged neatly and regular, but there was no obvious change compared with the control group. Endoplasmic reticulum dilation and Golgi body hypertrophy appeared in dexamethasone group and ethanol group. 瀛曟湡鍦板�炵背鏉炬毚闇插悾�

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