抑郁症模型大鼠血清雌激素与海马5-HT的关系

［摘要］目的　观察抑郁症模型大鼠血清雌二醇(E2)水平，海马5-羟色胺(5-HT)含量及其中缝核雌激素受体β(ERβ)和色氨酸羟化酶2(TPH2)表达的变化，探讨抑郁症发生的可能机制。方法　雌性SD大鼠，给予孤养和21d慢性不可预见性温和刺激(CUMS)制备抑郁症大鼠模型。采用放射免疫分析法(RIA)测定血清雌二醇(E2)水平、高效液相色谱-电化学检测法(HPLC-ECD)测定海马5-羟色胺(5-HT)含量，RTPCR技术检测中缝核ERβmRNA和TPH2 mRNA表达以及荧光免疫组化双重染色法检测中缝核ERβ蛋白和TPH2蛋白表达。结果　21d应激后，模型组大鼠血清E2水平下降、海马5-HT含量减少、中缝核ERβmRNA和TPH2 mRNA相对表达量下降及ERβ阳性细胞数和TPH2阳性细胞数明显减少。结论　E2与海马5-HT之间可能存在功能作用链—E2→中缝核5-HT能神经元ERβ→TPH2→海马5-HT。

［关键词］慢性不可预见性温和刺激；抑郁症；雌二醇；雌激素受体；5-羟色胺；色氨酸羟化酶2

The relationship between serum estradiol and hippocampal 5-HT in rat depression model

［Abstract］Objective In order to explore the mechanism of depression，we observed changes of serum estradiol，the concentration of 5-hydroxytryptamine(5-HT)in hippocampus and the expression of estrogen receptorβ(ERβ)and tryptophan hydroxylase 2(TPH2)in median raphe nuclei in depression model rats.Methods The animal model was established by giving isolation-housing in combination with 21 days of chronic unexpected mild stress(CUMS).Serum estradiol(E2)was measured by radio-immunoassay(RIA)，Hippocampal 5-HT content was determined by high performance liquid chromatogram-electrochemical de-tection(HPLC-ECD).The relative expression of ERβmRNA or TPH2 mRNA was estimated with hemi-quantitative reverse transcription-polymerase chain reaction(RT-PCR)technique，and the number of ERβor TPH2 immunoreactive neurons and their colocation state were detected with dual-label immunofluorescence method.Results After 21 days of CUMS，the level of serum E2 was lowered in rats of model group，the concentration of 5-HT in hippocampus was decreased，and the relative expression of ERβmRNA，TPH2 mRNA and numbers of ERβand TPH2 immunoreactive neurons in raphe nuclei were decreased as well.Conclusion In depression，the effect of E2 on 5-HT might be mediated through ERβand TPH2 in the raphe nuclei，and then led to affect 5-HT content in hippocampus.(www.xing528.com)

［Key words］chronic unexpected mild stress；depression；estrodiol；estrogen receptor；5-hydroxytryptamine；tryptophan hydroxylase 2

世界范围内女性抑郁症的发生率是男性的1.5～3.0倍。出现这种差异的原因尚不清楚，多数认为与性激素的作用有关。有研究发现，抑郁症与雌激素水平下降有明显的相关性，经补充雌激素取得了一定的疗效［1］，因此，性激素可能在情感性疾病发生中起重要作用。另外，抑郁症的发病机制不明，一般认为与中枢单胺类神经递质，尤其是5-羟色胺(5-HT)失调有关。关于抑郁症模型大鼠血清雌二醇(E2)水平与海马5-HT含量如何变化以及二者之间有何联系的研究少见报道。有研究表明，雌激素受体(ER)是抑郁症治疗中的一个主要调节因素［2］，雌激素(E)通过 ER［3，4］，但主要是 ERβ调节 5-HT系统而发挥抗抑郁作用［2，3］。许多研究显示：小鼠 5-HT神经元上含有 ERα和 ERβ［3，4］；大鼠5-HT神经元上是否有ERβ表达还存在争议［5，6，7］。色氨酸羟化酶2(TPH2)是2003年由德国的一个研究小组首先发现的第二种色氨酸羟化酶(TPH)，是5-HT合成过程中的限速酶，主要存在于脑中［8］。本研究旨在探讨E2与5-HT之间的联系，为抑郁症发病机制的研究提供科学依据。