【作者】 薛刚；

【导师】 张惠云；

【作者基本信息】 山东中医药大学 ， 中药学， 2011， 硕士

【摘要】 目的:制备愤怒郁怒情绪反应大鼠模型,研究模型评价指标;检测动物体内相关递质、激素水平变化,初步探讨愤怒郁怒产生机理及药物干预可能机制。方法:用社会隔离(Social Isolation Paradigm)加居住入侵法(Resident Intruder Test)诱导愤怒情绪反应大鼠模型,以攻击行为测试为主,辅以旷场实验和糖水偏好测试区分怒情绪的两种亚型(愤怒、郁怒),并随之考察造模方法稳定性,然后进行药物干预。造模结束后收集血清及分离额叶皮质、顶区皮质、海马、下丘脑四个脑区。以放免法和HPLC分别检测ACTH、Cor、T、NE、DA、5-HT、GABA含量。结果:⑴与正常对照组相比,造模后第2周攻击行为得分高组(HA)和攻击行为得分低组(LA)大鼠体质量均显著降低(P<0.001);HA组和LA组大鼠肾上腺系数也显著增加(P<0.01)。⑵攻击行为测试中,在两个周的造模时间内,HA组大鼠较LA组大鼠混合攻击行为得分显著增多(P<0.001, P<0.001),潜伏期显著缩短(P<0.001, P<0.001);旷场实验中,HA组、LA组与正常对照组相比,实验得分显著增多(P<0.01),且HA组大鼠得分与LA组相比亦显著增加(P<0.05);HA组、LA组的糖水偏好系数比正常对照组显著降低(P<0.01),但HA组、LA组大鼠之间无差别。⑶大鼠模型微观指标检测方面,大鼠血清Cor含量,愤模组较郁模组相比,显著下降(P<0.01);大鼠血清5-HT含量愤模组较郁模组显著上升(P<0.05);给药后,愤药组与愤模组大鼠相比,血清5-HT含量异常波动得到明显纠正(P<0.05),血清中DA和NE没有显著性差异。与正常对照组相比,愤模组大鼠下丘脑NE含量显著下降(P<0.001),郁模组大鼠顶区皮质、海马NE含量显著上升(P<0.001,P<0.001),而下丘脑NE含量则显著下降(P<0.001)。愤模组与郁模组相比,大鼠顶区皮质、额叶皮质、海马NE含量显著下降(P<0.01,P<0.01,P<0.01),而下丘脑NE含量显著上升(P<0.001),给药后愤药组大鼠额叶皮质NE含量异常变化得以纠正(P<0.05)。与正常对照组相比,愤模组额叶皮质、顶区皮质、海马DA含量显著下降(P<0.001,P<0.001,P<0.001),而下丘脑DA含量则显著上升(P<0.001),给药后下丘脑DA含量恢复至正常水平(P<0.001)。与正常对照组相比,郁模组额叶皮质DA含量显著降低(P<0.001),而下丘脑DA含量则显著上升(P<0.001),药物干预后,下丘脑DA含量恢复至正常水平(P<0.05)。愤模组与郁模组相比,大鼠顶区皮质、海马DA含量显著下降(P<0.001,P<0.001)。与正常对照组相比,愤模组大鼠下丘脑5-HT含量显著降低(P<0.001)。与正常对照组相比,郁模组大鼠额叶皮质5-HT含量显著上升(P<0.05),而下丘脑5-HT含量则显著下降(P<0.001),给药后下丘脑5-HT含量得到明显纠正(P<0.001)。愤模组与郁模组相比,大鼠下丘脑5-HT含量显著上升(P<0.05)。结论:利用社会隔离加居住入侵法可成功制备愤怒郁怒情绪反应大鼠模型。造模方法可靠,具有较好的可信度及可重复性;应用攻击行为测试可明确区分愤怒郁怒情绪反应。①大鼠愤怒情绪反应与下丘脑NE含量下降,额叶皮质、顶区皮质、海马DA、下丘脑5-HT含量显著下降,下丘脑DA含量显著上升有关。②大鼠郁怒情绪反应与大鼠顶区皮质、海马NE、下丘脑DA、额叶皮质5-HT含量显著上升,下丘脑5-HT、NE、额叶皮质DA含量下降有关。因此我们可推断干预药物经前平颗粒、经前舒颗粒可能通过纠正上述指标异常变化而发挥药理作用,作用关键部位是中枢不同脑区。更多还原

【Abstract】 Objective: Our aims of this study are to introduce rat model and research evaluative method of anger-out/in emotional reaction, to investigate changes of neurotransmitter and hormone and to initially explore the mechanism of rat model as well as effect of medicine.Methods: Model rats with anger-out/in emotional reaction are induced by social isolation paradigm plus resident intruder stress, after that we distinguished the difference between angry-out and anger-in by aggressive behavior test, supplemented by open-field test and sugar preference test, subsequently examine the stability of the modeling method, and then intervened with Jingqianping (Jingqianshu) granule. After model establishment,we killed the rats by decapitation,collected serum and dissected different brain regions(prefrontal cortex, parietal cortex, hippocampus and hypothalamus), detected ACTH, Cor, T,NE,DA,5-HT and GABA content with radioimmunoassay and high-performance liquid chromatography .Results:⑴Compared with the normal group, the body weight of high aggressive(HA) and low aggressive(LA) rats lessened significantly(P<0.001),while drenal glands coefficient of HA and LA rats’reduced (P<0.01).⑵In aggressive behavior test, composite aggressive counts of HA rats were significantly higher than LA(P<0.001, P<0.001),latent time of attack were lower(P<0.001, P<0.001);In open-field experiment HA/LA rats’total scores were also higher than controlled (P<0.01), and HA rats’higher than LA’s, while comparison result of sugar preference coefficients contrary to it (P<0.01);⑶Compared with anger-in group, Cor contents in serum of anger-out model rats descended notably(P<0.01),while NE contents increased(P<0.05); After administrated with Jingqianping (Jingqianshu) granule, abnormal fluctuations of 5-HT are obviously corrected between anger-out and anger-in (P<0.05).Compared with the control group, NE contents in hypothalamus, parietal region and hippocampus of anger model decreased (P<0.001), while DA contents in hypothalamus, and then restored after administration. Unlikely, DA contents in prefrontal cortex decreased (P<0.01), but increased in hypothalamus, they could both be corrected after administration. DA contents of anger-out model rats in prefrontal cortex and hippocampus were lower than anger-in group (P<0.001).Compared with the control group, 5-HT contents in hypothalamus of anger model rats degraded significantly (P<0.001), while increased in prefrontal cortex and decreased in hypothalamus, the abnormality disappeared after administration. 5-HT contents of anger-out model group in hypothalamus were obviously higher than anger-in group (P<0.05).Conclusion: The anger-out/in emotional reaction rat model can be introduced by the method of social isolation plus resident intruder stress. Modeling method was reliable and mature with a better credibility and repeatability; Adopting method aggressive behavior could distinguish anger-out/in belongings of rats’model clearly.Parts of the microcosmic mechanism were disclosed: anger-out emotion maybe related to NE, 5-HT level descending in hypothalamus, DA level descending in prefrontal cortex, parietal cortex and hippocampus, DA level increasing hypothalamus;while anger-in emotion maybe related to NE level increasing in parietal cortex and hippocampus,DA level increasing in hypothalamus, 5-HT level increasing in prefrontal cortex, 5-HT,NE level descending in hypothalamus, DA level descending in prefrontal cortex. We can assume that Jingqianping (Jingqianshu) granule play the role of pharmacological effects by corrected those indicators and its possible function location is different cerebral regions.更多还原