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不同时期产前应激对大鼠子代行为学及分子生物学的影响

发布时间:2018-10-20 08:24
【摘要】:目的 本实验通过建立两个不同时期的产前应激大鼠动物模型,观察不同时期产前应激对子代大鼠的行为学、细胞因子白介素18 (interleukin 18, IL-18)及细胞外信号调节激酶(Mitogn activated protein kinase kinase 1, MEK-1)的影响,从而探讨产前应激敏感期及性别效应的病理生理机制,以期为与产前应激相关的疾病的发病机制的研究提供依据。 方法 将SD妊娠大鼠随机分成3组,对照组在妊娠期间不给予任何刺激;中期应激组在从妊娠第9-14天给予束缚刺激;晚期妊娠组从妊娠第15-20天给予束缚刺激。待子代出生后第21天断奶并将雌雄大鼠分笼饲养。子代成年后即出生后第75天分别进行敞箱实验、新事物实验、蔗糖喜爱实验、前脉冲抑制及惊恐反射实验和强迫游泳实验5种行为学测试及检测大鼠海马的IL-18和MEK-1。 结果 一.行为学实验结果: 1.敞箱实验:结果显示与对照组雄性子代相比孕晚期产前刺激雄性子代的敞箱总路程减少(p0.05),中央区域总路程减少(p0.05),中央区域停留时间减少(p0.01)。 2.新事物实验:结果显示与对照组雄性子代接触新事物的时间相比孕中期产期应激组雄性子代(p0.01)及孕晚期产期应激组雄性子代(p0.05)均减少。 3.糖水消耗实验:结果显示与对照组雄性子代相比孕中期产前应激组雄性子代平均体重糖水消耗量降低(p0.05)。 4.前脉冲及惊恐抑制实验:结果显示在前脉冲抑制反应中孕中期产前应激组子代与对照组子代相比反应减低(p0.05);在惊恐反应孕晚期产前应激子代与对照组子代相比反应增高(p0.01)。 5.强迫游泳实验:结果显示与对照组子代相比孕晚期的产前应激组雌子代(p0.05)和雄性子代(p0.01)的“绝望”行为增加,而孕中期产前应激组仅雄性子代大鼠“绝望”行为增加(p0.05)。 二.背侧海马和腹侧海马的IL-18含量及MEK-1阳性细胞检测结果: 1.IL-18结果显示与对照组相比孕晚期产前应激可导致雌性子代的腹侧海马IL-18含量增加(p0.05),而孕中期产前应激对子代海马IL-18含量的无影响(p0.05)。 2.MEK-1阳性细胞结果显示与对照组相比孕晚期可以导致背侧海马MEK-1的表达增加(p0.01)及腹侧海马MEK-1的表达下降(p0.05),而孕中期对海马的MEK-1的表达无影响(p0.05)。 结论 1.孕中期和孕晚期产期应激均可导致子代行为学的改变,但孕晚期产前应激对子代行为学的影响更多。 2.不同性别的产前应激子代大鼠行为学改变存在差异,产前应激对雄性子代的影响高于对雌性子代的影响。 3.孕晚期产前应激可导致子代大鼠海马的炎性因子IL-18分泌增加及MEK-1信号蛋白表达异常。 4.腹侧和背侧海马的“功能分离”可能与MEK-1信号蛋白的表达及其相关的丝裂原活化蛋白激酶(Mitogen-activated protein kinases, MAPKs)信号传导途径有关。 5.IL-18可能参与MEK-1信号蛋白的表达的调控。
[Abstract]:Purpose In this study, we established animal models of pre-production stress rats in different periods, observed the behavior of pre-stress on filial generation in different periods, cytokine interleukin 18 (IL-18) and extracellular signal regulated kinase (MEK-1). Effects of pre-production stress-sensitive period and gender effect on the pathogenesis of pre-production stress-related diseases were discussed. for the purposes of According to the method, SD pregnant rats were randomly divided into 3 groups, and the control group did not give any stimulation during pregnancy; the medium-term stress group was subjected to binding stimulation from 9 to 14 days of pregnancy; and the late pregnancy group was from the first trimester of pregnancy. 5-20 days of restraint irritation. On Day 21 after birth of children The male and female rats were fed with milk and the male and female rats were fed into cage. The children were born on the 75th day after birth. The experiment of new things, sucrose favorite experiment, pre-pulse suppression and panic reflex experiment and forced swimming experiment were carried out. 5 behavioral tests were carried out and the hippocampus of rats were tested. IL -1 8 and MEK-1. Results: 1. The results of behavioral experiment: The results showed that the total distance of male offspring stimulated male offspring was decreased (P0.05) compared with the male offspring of the control group, and the total distance of the central region was decreased (p 0. 05), the central region dwell time was decreased (P0.01). 2. New things experiment: The results showed that male offspring in the middle of the pregnancy were compared to male offspring of the control group (n. The results showed that the male offspring of the control group were compared with those in the control group. The average body weight loss of male offspring in the pre-pregnant stress group was lower than that in the pre-pregnant stress group (P0.05). The results showed that the offspring of the pre-pregnant stress group and the offspring of the control group were lower than that of the control group (P0.05). The results showed that compared with the offspring of the control group, the 鈥渄espair鈥,

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