生地黄抗抑郁性别差异研究  

Gender differences in antidepressant effect of raw Rehmanniae Radix

作　　者：巫晓慧 王君明[1,2] 秦玲玉 张天柱 李亚敏 张月月[1] 龙冰玉 何庆文 纪丽婕 宋玲玲 WU Xiao-hui;WANG Jun-ming;QIN Ling-yu;ZHANG Tian-zhu;LI Ya-min;ZHANG Yue-yue;LONG Bing-yu;HE Qing-wen;JI Li-jie;SONG Ling-ling(School of Pharmacy,Henan University of Chinese Medicine,Zhengzhou 450046,China;Collaborative Innovation Center for Respiratory Disease Diagnosis and Treatment&Chinese Medicine Development of Henan Province,Henan University of Chinese Medicine,Zhengzhou 450046,China)

机构地区：[1]河南中医药大学药学院,河南郑州450046 [2]河南中医药大学呼吸疾病中医药防治省部共建协同创新中心,河南郑州450046

出　　处：《中国中药杂志》2023年第19期5326-5336,共11页China Journal of Chinese Materia Medica

基　　金：河南省自然科学基金杰出青年基金项目(232300421012);河南省级科技研发计划联合基金(优势学科培育类)项目(222301420085);国家自然科学基金面上项目(82374068)。

摘　　要：该文首次基于复合中医阴虚内热证型的经典抑郁症模型评价生地黄抗抑郁作用的性别差异特点及其机制。采用目前相对更公认也是应用最广的甲状腺素致阴虚内热模型复合经典抑郁症模型(慢性不可预见性温和应激模型)综合建立阴虚内热证型抑郁症模型,并利用雌、雄小鼠同时给药,结合对雌、雄动物滋阴清热指标、常规抗抑郁药效测试指标、反映抑郁症发病和防治机制的一些重要生物分子的检测分析及抗抑郁药效与滋阴清热功效和生物机制的关联分析,综合评定生地黄对于阴虚内热证型抑郁症的抗抑郁作用性别差异特点及其机制。生地黄对雌、雄模型小鼠都表现出抗抑郁作用且其抗抑郁效果表现出性别差异性,其中对雌性的抗抑郁效果优于雄性;生地黄对雌性海马神经元损伤、神经核阳性区域、突触后致密区蛋白95和突触素的蛋白表达升高效果优于雄性。此外,给药生地黄还显著逆转雌、雄模型小鼠海马核因子(NF)-κB/环氧合酶2(COX2)/NOD样受体热蛋白结构域相关蛋白3(NLRP3)通路蛋白表达的异常上调。生地黄对于雌性阴虚内热证型抑郁症模型小鼠的抗抑郁效果优于雄性,其抗抑郁性别差异机制可能涉及改善神经元损伤并增强神经可塑性;生地黄对于阴虚内热证型抑郁症的抗抑郁机制可能与下调NF-κB/COX2/NLRP3通路以减少神经元损伤并增强神经可塑性有关。For the first time,this study evaluated the gender differences and mechanisms of the antidepressant effects of raw Rehmanniae Radix(RRR) based on the classic depression model with traditional Chinese medicine syndrome of Yin deficiency and internal heat.The depression model with Yin deficiency and internal heat was established by the widely recognized and applied method of thyroxine induction of the classic depression model with Yin deficiency and internal heat(chronic unpredictable mild stress).Male and female mice were simultaneously treated with RRR.The study analyzed indicators of nourishing Yin and clearing heat,conventional antidepressant efficacy test indicators,and important biomolecules reflecting the pathogenesis and prevention and treatment mechanisms of depression,and conducted a correlation analysis of antidepressant efficacy,Yin-nourishing and heat-clearing efficacy,and biological mechanism in different genders,thereby comprehensively assessing the antidepressant effects of RRR on depression of Yin deficiency and internal heat,as well as its gender differences and mechanisms.RRR exhibited antidepressant effects in both male and female mouse models,and its antidepressant efficacy showed gender differences,with a superior effect observed in females.Moreover,the effects of RRR on enhancing or improving hippocampal neuronal pathology,nucleus-positive areas,postsynaptic dense area protein 95,and synaptophysin protein expression were more significant in females than in males.In addition,RRR significantly reversed the abnormal upregulation of nuclear factor(NF)-κB/cyclooxygenase 2(COX2)/NOD-like receptor thermal protein domain associated protein 3(NLRP3) pathway proteins in the hippocampus of both male and female mouse models.The antidepressant effects of RRR were more pronounced in depression female mice with Yin deficiency and internal heat syndrome,possibly due to the improvement of neuronal damage and enhancement of neuroplasticity.The antidepressant mechanisms of RRR for depression with Yin deficienc

关 键 词：性别差异 生地黄 阴虚内热型抑郁症 抗抑郁 滋阴清热 神经可塑性 

分 类 号：R285.5[医药卫生—中药学]