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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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