摘要
本研究旨在探讨肉苁蓉苯乙醇苷(Cistanche phenylethanol glycosides,CPhGs)对慢性不可预知温和应激(chronic unpredictable mild stress,CUMS)诱导的小鼠抑郁样行为的治疗效果及其机制。将小鼠随机分为空白组、模型组、CPhGs高剂量组(700 mg/kg)、CPhGs中剂量组(350 mg/kg)、CPhGs低剂量组(175 mg/kg)和氟西汀组(15 mg/kg)。给予相应药物干预4周后,进行神经行为学测试;酶联免疫法检测血清中神经递质水平、海马组织中炎症因子和炎症介质含量;苏木精-伊红染色和尼氏染色观察海马组织病理变化;采用免疫组织化学和免疫荧光法分析小鼠海马组织中星形胶质细胞和小胶质细胞密度,以及类Toll受体4(toll-like receptor 4,TLR4)、核因子κB(nuclear factorκB,NF-κB)和Nod样受体蛋白3(Nod-like receptor protein 3,NLRP3)的表达水平。结果显示,CPhGs能改善小鼠抑郁样行为,提高糖水偏好率和减少不动时间,显著增强了小鼠血清中的5-羟色胺和多巴胺水平,抑制海马中炎症介质和因子的表达。免疫组织化学分析表明,CPhGs可增加海马星形胶质细胞的密度,减少小胶质细胞的激活,并抑制NLRP3炎症小体相关蛋白的表达。免疫荧光实验结果表明CPhGs减少炎症小体形成的作用机制是降低海马组织中TLR4/NF-κB信号通路的活化。综上所述,CPhGs对CUMS诱导的抑郁样行为表现出明显的抗抑郁作用,其机制可能是通过调节神经递质水平与抑制神经炎症反应,该研究为其在抑郁症治疗中的应用提供了实验依据。
This study aims to investigate the therapeutic effects and mechanisms of Cistanche phenylethanol glycosides(CPhGs)on depression-like behavior induced by chronic unpredictable mild stress(CUMS)in mice.Mice were randomly divided into control group,model group,high dose CPhGs group(700 mg/kg),middle dose CPhGs group(350 mg/kg),low dose CPhGs group(175 mg/kg),and fluoxetine group(15 mg/kg).After four weeks of corresponding drug interventions,neurobehavioral tests were conducted;enzyme-linked immunosorbent assay was used to detect levels of neurotransmitters in serum,as well as the content of inflammatory factors and mediators in hippocampal tissue.Hematoxylin-eosin and Nissl staining were employed to observe pathological changes in hippocampal tissue.Immunohistochemistry and immunofluorescence methods were used to analyze the density of astrocytes and microglia in the hippocampal tissue of mice,as well as the expression levels of toll-like receptor 4/nuclear factorκB/Nod-like receptor protein 3(TLR4/NF-κB/NLRP3).Results showed that CPhGs could improve depression-like behavior in mice,increase the preference for sweet water,and reduce immobility time,significantly enhancing the levels of serotonin and dopamine in mouse serum,while inhibiting the expression of inflammatory mediators and factors in the hippocampus.Immunohistochemical analysis indicated that CPhGs could increase the density of astrocytes in the hippocampus,reduce the activation of microglia,and inhibit the expression of NLRP3 inflammasome-related proteins.Immunofluorescence experiments demonstrated that the mechanism through which CPhGs reduce inflammasome formation was by decreasing the activation of the TLR4/NF-κB signaling pathway in hippocampal tissue.In summary,CPhGs exhibit significant antidepressant effects on CUMS-induced depression-like behavior,potentially through the regulation of neurotransmitter levels and inhibition of neuroinflammatory responses,providing experimental evidence for its application in the treatment of depression.
作者
郝梅
李红艳
HAO Mei;LI Hong-yan(Mental Health Education Center,Henan Quality Institute;Department of Chemical Engineering and Food Science,Henan Quality Institute,Pingdingshan 467000,China)
出处
《天然产物研究与开发》
北大核心
2025年第2期204-214,327,共12页
Natural Product Research and Development
基金
河南省高等教育教学改革研究与实践项目(2024SJGLX0730)。
