经前舒颗粒通过调节食欲素信号缓解经前抑郁症。
Jingqianshu granules mitigates premenstrual depression by regulating orexin signaling.
发表日期:2024
作者:
Ping Dong, Weibo Dai, Tingting Zhao, Yuandong Gong, Ning Weng, Shimeng Lv, Yifan Zhao, Chunyu Du, Yuexiang Ma, Zhen Zhang, Shuhua He, Feng Zheng, Peng Sun
来源:
Frontiers in Pharmacology
摘要:
简介:经前烦躁障碍 (PMDD) 是经前综合症 (PMS) 的一种严重形式,是一种影响患者情绪的严重健康障碍。它是由周期性心理症状引起的,其发病机制尚不清楚。基底外侧杏仁核(BLA)食欲素系统异常是抑郁情绪发生的重要原因,但在经前抑郁症(PMDD)中尚未见报道,因此探讨其内在机制对于丰富经前抑郁症(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荆千舒颗粒的活性成分。使用强迫游泳试验(FST)建立经前抑郁症大鼠模型。该实验由两部分组成。第一部分将大鼠分为对照组、模型组、模型经前舒组、模型氟西汀组。采用FST、旷场试验和高架十字迷宫试验来评估大鼠的行为以及药物干预的效果。采用免疫荧光和RT-qPCR检测orexin及其受体OX1R和OX2R基因和蛋白的表达。 Western-Blot检测BLA脑区Toll样受体4、核因子κ-B、肿瘤坏死因子-α、白细胞介素6、白细胞介素1β的表达。在第二部分中,向大鼠脑内注射食欲素-A。观察对照组、模型组、模型食欲素A组大鼠行为学活动。采用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:荆千舒颗粒的5种成分为:芍药苷、芥酸、甘草苷、橙皮苷、丹皮酚。在动情周期中,大鼠在行为测试的非接受期表现出抑郁样行为,这种行为在接受期消失。免疫荧光和RT-qPCR显示模型组大鼠BLA区食欲素、OX1R和OX2R基因和蛋白表达降低。WB显示炎症因子水平升高。药物治疗后全部恢复至控制水平。在第二部分中,将食欲素-A注射到模型大鼠的BLA脑区导致小胶质细胞的免疫反应性降低和炎症因子的表达水平降低。讨论:健前舒颗粒可通过调节食欲素介导的炎症因子达到治疗经前抑郁症的目的,为进一步研究经前抑郁症的发病机制提供了新思路。然而,目前的研究仍处于初步阶段,PMDD的发病机制较为复杂。因此,需要更深入的探索。版权所有 © 2024 董、戴、赵、龚、翁、吕、赵、杜、马、张、何、郑、孙。
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.Copyright © 2024 Dong, Dai, Zhao, Gong, Weng, Lv, Zhao, Du, Ma, Zhang, He, Zheng and Sun.