第五节 神经免疫内分泌调节环路
各种生物活性物质对神经、免疫、内分泌三大系统的作用不是独立进行的，整体条件下基本是以较完整的环路为单位，构成复杂的网络。这些环路的工作方式是正反馈和负反馈，有调节精确、放大效应、整合效应、自限性及级联反应等特点。以下例举几种典型的神经内分泌免疫调节环路。
（一）下丘脑-垂体前叶-肾上腺皮质与Mo-Mφ环路（HPA-Mo/Mφ）
此环路的中心成分为CRH-ACTH-GC-IL-1。具体环节如下：
（1）下丘脑的CRH促进垂体前叶释放ACTH，后者刺激GC大量分泌，引起血中GC浓度升高。（2）ACTH及GC可分别抑制Mo-Mφ的功能，减少IL-1的生成。
（3）受刺激后活化的Mo-Mφ生成IL-1增加，而IL-1则作用于下丘脑促进CRH释放，作用于垂体前叶诱导ACTH的分泌，也有报导IL-1直接刺激肾上腺皮质分泌GC。
（4）ACTH有GC限制IL-1的进一步生成，且ACTH前体POMC还可裂解释放α-MSH，而α-MSH可在中枢水平对抗IL-1对CRH分泌的刺激效应。见图10-5。
图10-5 HPA与Mo-Mφ轴系
注：+兴奋 -抑制
（二）下丘脑-垂体前叶-肾上腺皮质与胸膛环路
此环路有如下环节：
（1）HPA轴中ACTH和GC均可抑制胸腺的功能，包括细胞增殖及胸膛激素分泌。
（2）胸腺激素中thymosin α1及thymulin等都能刺激ACTH的分泌。
（3）胸腺中含CRH受体并可合成CRH，而CRH对胸腺的某些功能有刺激效应。见图10-6。
图10-6 HPA与胸腺轴系
（三）下丘脑-垂体前叶与胸腺环路
（1）下丘脑分泌GHRH、PRF和TRH，作用于垂体前叶，刺激GH和PRL的分泌。
（2）GH和PRL影响胸腺的发育、细胞的功能及激素的合成，胸腺中可合成GH、PRL。
（3）胸腺肽可刺激GH及PRL从垂体前叶释放。
（四）下丘脑-垂体前叶-性腺轴系与胸腺环路
（1）LHRH刺激垂体前叶释放LH/FSH，二者引起性腺分泌雄激素、雌激素及孕激素。
（2）这些类固醇激素对胸腺功能有较强的抑制性效应，如使胸腺体积减少、细胞数目减少、细胞免疫功能障碍等。
（3）胸腺肽中thymosin β4可在离体条件下刺激下丘脑释放LHRH。
（4）胸腺还可分泌一种蛋白成分，强有力地抑制性腺分泌性激素。
（5）LHRH也可由胸遥小皮细胞合成。
（6）卵巢中有thymosin原的存在。
图10-7 下丘脑-垂体前体与胸腺环路
图10-8 HPG与胸腺的联系
神经、免疫和内分泌系统间有经常性的信息往返交流，此种联系对各系统的生理功能是必不可少的。由于三大系统均共享各种生物活性物质，如GH和PRL既是神经内分泌激素，也可视为免疫因子，而IL-1或IL-2也可称做神经介质或神经派往素亦不为过。因此，众多信息分子的原有命名已不足以恰当概括其多重活性。免疫系统可感觉机体内环境的理化和生物性改变，同时还可能具备对感受的信息进行加工、处理、存贮及整合等功能，这引起特点与神经系统有一定的相似性。免疫功能的执行服从于整体需求，如在应激条件下，免疫系统活动减弱，以保证机体充分应付与生存悠关的体内外各种条件改变。再如妊娠时，保持胎盘的免疫抑制状态，有利于胚胎的顺利发育。已在众多疾病的病理及病理生理过程中，找到神经免疫内分泌交互作用的证据。相信随着研究的深入，必将提示更多疾病与神经免疫内分泌网络的联系，从而为临床的诊治提供新的思路、手段和药物。神经免疫内分泌学的研究也将有助于提示脑的奥秘。
（张万会）
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