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抑郁症是一种使人衰弱的精神障碍,其特征是持续情绪低落,对几乎所有活动都失去兴趣或愉悦感,并与疲劳、睡眠障碍、焦虑和神经认知障碍症状有关[1],是全球残疾的第三大原因。抑郁症患者工作低下、具有较高的自杀倾向,严重影响患者的生活,造成沉重的社会经济负担[2]。由于疫情的影响,社会心理健康问题正在急剧增加[3,4]。目前,临床上使用的大多数抗抑郁药都具有耐药性,并伴有各种不良反应。因此,寻找安全性更高、不良反应更少的抑郁症治疗方法具有重要意义。既往研究表明,炎症反应在抑郁症中起着至关重要的作用[5]。抑郁症患者血液及额叶皮层中的促炎细胞因子增加[6,7]。抗炎治疗可以产生抗抑郁作用,而抗抑郁药可以减弱抑郁症中促炎细胞因子的表达[8,9]。因此,抑制神经炎症是治疗抑郁症的重要方向。
百合知母汤是中国东汉张仲景医典《金匮要略》中记载的一种经典中药方剂,用于治疗“百合病”[10]。中医“百合病”被认为与现代抑郁症的表现具有较高的相似性[11]。目前,百合知母汤在中医临床上被广泛用于治疗抑郁症[12]。药理学研究表明,百合知母汤在动物模型中具有显著的抗抑郁作用[13]。然而,百合知母汤治疗抑郁症的作用机制并未完全明了。前期研究发现百合知母汤能够通过抑制CUMS抑郁模型小鼠的神经炎症,降低海马IL-1β、 IL-6和TNF-α等促炎细胞因子的表达,来发挥抗抑郁作用[14]。鉴于NLRP1炎症小体在炎症反应过程中的重要的作用[15],且最近研究发现NLRP1炎症小体在抑郁症的发展过程中扮演重用角色[16]。该研究基于NLRP1炎症小体的活化,对百合知母汤的抗抑郁作用进行进一步的探索。
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