PDF(Pubmed)
Abstract：
Introduction: Premenstrual dysphoric disorder (PMDD), a severe form of premenstrual syndrome (PMS), is a serious health disorder that affects patient moods. It is caused by cyclic psychological symptoms and its pathogenesis is still unclear. Abnormalities in the basolateral amygdala (BLA) orexin system, which are important causes of the development of depressive mood, have not been reported in PMDD, so exploring its intrinsic mechanisms is meaningful for enriching the pathomechanisms of PMDD. Methods: High performance liquid chromatography was used for the determination of the active ingredients of Jingqianshu granules. Developing a rat model of premenstrual depression using the forced swimming test (FST). The experiment consisted of two parts. In Part 1, the rats were divided into the control group, the model group, the model + Jingqianshu group, and the model + fluoxetine group. The FST, open field test, and elevated plus maze test, were used to assess the behavior of the rats as well as to evaluate the effect of drug intervention. Immunofluorescence and RT-qPCR were used to detect the expression of orexin and its receptors OX1R and OX2R genes and proteins. The expression of Toll-like receptor 4, nuclear factor kappa-B, tumor necrosis factor-α, interleukin 6, and interleukin-1β in the BLA brain region was detected by Western-Blot. In part 2, the rats were injected intracerebrally with orexin-A. Observe the behavioral activities of rats in the control group, model group, and model+orexin-A group. Immunofluorescence was used to detect microglia in the BLA area of rats, and the expression levels of the above inflammatory factors were detected by Western-Blot. Results: The five components of Jingqianshu granules are: paeoniflorin, erulic acid, liquiritin, hesperidin, and paeonol. During the estrous cycle, rats exhibited depressive-like behavior during the non-receptive phase of the behavioral test, which disappeared during the receptive phase. Immunofluorescence and RT-qPCR showed reduced gene and protein expression of orexin, OX1R, and OX2R in the BLA region of rats in the model group.WB showed elevated levels of inflammatory factors. All returned to control levels after drug treatment. In part 2, injection of orexin-A into the BLA brain region of model rats resulted in reduced immunoreactivity of microglia and decreased expression levels of inflammatory factors. Discussion: Jianqianshu granules can achieve the purpose of treating premenstrual depression by regulating orexin-mediated inflammatory factors, which provides a new idea for further research on the pathogenesis of PMDD. However, the current study is still preliminary and the pathogenesis of PMDD is complex. Therefore, more in-depth exploration is needed.
摘要：
简介：经前烦躁不安症（PMDD），一种严重的经前期综合征（PMS），是一种严重的健康失调，影响病人的情绪。它是由周期性的心理症状引起的，其发病机制尚不清楚。基底外侧杏仁核（BLA）食欲素系统异常，这是抑郁情绪发展的重要原因，在PMDD中没有报告，因此，探索其内在机制对于丰富PMDD的发病机制具有重要意义。方法:采用高效液相色谱法测定经前舒颗粒的有效成分含量。使用强迫游泳测试（FST）开发经前抑郁的大鼠模型。实验由两部分组成。在第一部分中，将大鼠分为对照组，模型组，模型+静千舒组，模型+氟西汀组。FST,露天试验,高架加迷宫测试，用于评估大鼠的行为以及评估药物干预的效果。免疫荧光和RT-qPCR检测食欲素及其受体OX1R和OX2R基因和蛋白的表达。Toll样受体4、核因子κB的表达,肿瘤坏死因子-α，通过Western-Blot检测到BLA脑区的白介素6和白介素1β。在第2部分中，对大鼠脑内注射食欲素A。观察对照组大鼠的行为活动,模型组,模型+食欲素-A组。免疫荧光法检测大鼠BLA区小胶质细胞,Western-Blot检测上述炎症因子的表达水平。结果:经前舒颗粒的5个成分为:芍药苷,Erulicacid,甘草苷,橙皮苷,还有Paeonol.在发情周期中，大鼠在行为测试的非接受阶段表现出抑郁样行为，在接受阶段消失了。免疫荧光和RT-qPCR显示食欲素基因和蛋白表达降低，OX1R,模型组大鼠BLA区OX2R。WB显示炎症因子水平升高。药物治疗后全部恢复到对照水平。在第二部分中，向模型大鼠的BLA脑区注射食欲素A导致小胶质细胞的免疫反应性降低，炎症因子的表达水平降低。讨论:健前舒颗粒通过调节食欲素介导的炎症因子达到治疗经前期抑郁症的目的,为进一步研究PMDD的发病机制提供了新的思路。然而,PMDD的发病机制复杂,目前的研究尚处于初步阶段。因此,需要更深入的探索。
