色氨酸羟化酶2在更年期抑郁症大鼠中表达减少

［摘要］目的　观察更年期抑郁症大鼠模型海马5-羟色胺(5-HT)含量及其合成限速酶-色氨酸羟化酶2(TPH2)表达的变化。方法　雌性SD大鼠，在卵巢切除术的基础上，联合孤养和21d慢性不可预见性温和刺激(CUMS)制备更年期抑郁症大鼠模型，以行为学测试进行评价。用高效液相色谱-电化学法(HPLC-ECD)测定海马5-HT含量；用RT-PCR技术检测中缝核TPH2 mRNA表达量；用荧光免疫组化检测中缝核TPH2蛋白表达。结果　21d应激后，模型组大鼠直立活动得分及水平活动得分均减少，糖水消耗百分比下降；海马5-HT含量下降；中缝核TPH2 mRNA表达量及TPH2阳性神经元数量减少。结论　在卵巢切除术的基础上，联合孤养和21d CUMS可造成更年期抑郁症大鼠模型；模型大鼠海马5-HT含量下降，可能是中缝核TPH2的表达减少所致。

［关键词］慢性不可预见性温和刺激；5-羟色胺；色氨酸羟化酶2

Decreased expression of TPH2 in median raphe nuclei of perimenopausal depression model rats

［Abstract］Objective To explore changes of the concentration of 5-hydroxytryptamine(5-HT)in hippocampus and the expression of tryptophan hydroxylase 2(TPH2)in median raphe nuclei in the perimenopausal depression model rats.Methods The animal model was established by resecting the ovaries of female rats，then giving isolation-housing in combination with chronic unexpected mild stress(CUMS)for 21 days.Behavioral tests were used to evaluate the model.High performance liquid chromatogram-electrochemical detection was employed to measure 5-hydroxytryptamine(5-HT)in hippocampus.Reverse transcription-polymerase chain reaction(RT-PCR)and immunohistochemistry were to detect the relative expression of TPH2 mRNA and TPH2 immunoreactive neurons in median raphe nuclei.Results After 21 days ofCUMS，both crossing and rearing in model group were reduced in Open-field test，and percentage of sugar consumption was decreased too.The concentration of 5-HT in hippocampus was lowered in the model group，the relative expression of TPH2 mRNA and the number of TPH2 immunoreactive neurons in raphe nuclei were decreased too.Conclusion Perimenopausal depression model could successfully be induced by ovariectomy，isolation-housing in combination with 21 days of CUMS.The decrease of 5-HT in hippocampus might be through reducing the expression of TPH2 in median raphe nuclei，which leads to lower the synthesis of 5-HT.(www.xing528.com)

［Key words］chronic unexpected mild stress；5-hydroxytryptamine；tryptophan hydroxylase 2

更年期抑郁症是诸多抑郁症中的一种类型，是特指初次发病于更年期(也称围绝经期，是指从卵巢功能紊乱到绝经后1年)，以焦虑不安和情绪低落为主要症状的疾病，属于情感性精神障碍。随着生活节奏的加快，社会竞争的加剧，更年期抑郁症的发病率呈逐年上升趋势，逐渐成为人们研究的焦点。然而，该病发病机制不明，但许多研究认为与中枢单胺类神经递质，尤其是5-羟色胺(5-hydroxy-tryptamine，5-HT)含量改变有关。关于抑郁症脑内5-HT含量如何变化，报道不一。色氨酸羟化酶2(tryptophan hydroxylase 2，TPH2)是中枢5-HT合成的限速酶［1-2］。然而，关于更年期抑郁症中缝核TPH2表达变化的报道还不多见，因此，本研究采用雌性SD大鼠，在卵巢切除术的基础上，联合孤养和21d慢性不可预见性温和刺激(CUMS)制备更年期抑郁症大鼠模型，并观察大鼠海马5-HT的含量以及中缝核TPH2表达的情况，为更年期抑郁症的深入研究提供实验基础。