|Other Abstract|| 为探讨条件反射性免疫调节的神经学机制，采用腹腔内注射蛋白抗原卵清蛋白（OVA）作为非条件刺激物（UCS），糖精水为条件刺激物（CS），只经一次结合训练后，在初次抗体应答下降但仍保持一定水平时单独给予条件刺激，从而建立条件反射性抗体反应增高模型。并在条件刺激日及条件反射性抗体生成高峰期，用 c-fos 免疫组化技术对脑内神经元活动情况进行观察，从而探讨可能参与条件反射性抗体反应增高过程的脑结构。主要结果如下：|
1．一次条件训练后，单独给予条件刺激后约 15天左右出现明显的抗OVA抗体水平增高，20、25 天左右达到峰值，以后明显下降逐渐接近正常水平。这一过程与初次免疫应答的基本规律是类似的。
2. 免疫过的动物相比于未经免疫的动物其脑内有广泛的较强的 c-fos 蛋白表达，主要包括：丘脑（前背侧核、中央内侧核）；下丘脑（室旁核、前腹侧视前核、视交叉上核、外侧视前核、视上核及后核）；杏仁终纹复合体（杏仁基底内、外侧核、杏仁外侧核、杏仁中央核）；其它如额皮质、杏仁周皮质、嗅前皮质、压部后皮质、终纹下丘脑核等部位。
3. 经过 CS/UCS 结合性训练的动物相比于单纯免疫的动物，在杏仁终纹复合体（杏仁基底外侧核、杏仁外侧核、杏仁内侧核、杏仁中央核、外侧嗅束核、皮质杏仁、终纹床核），丘脑和下丘脑（外侧缰核、丘脑前背侧核、菱形核、室旁核、中央内侧核、中央旁核、下丘脑弓状核），岛叶皮质（岛颗粒皮质、岛乱颗粒皮质）及屏状核、斜角带、压部后皮质、扣带皮质、孤束核、下橄榄内侧核、中缝苍白核等结构内有较强的c-fos 表达。
4. 条件训练后再次单独给予 CS的动物与未给 CS的动物相比，主要在岛叶皮质（岛无颗粒皮质、岛乱颗粒皮质、岛颗粒皮质）、丘脑室旁核和菱形核、正中隆起、最后区、中缝苍白核和孤束核等结构内有较强的c-fos 表达。
5. 条件刺激后 20 天，条件反射组动物的抗 OVA 抗体水平显著高于对照组，在某些脑区内c-fos 蛋白表达也相应地强于对照组，这些脑区包括：岛颗粒皮质、孤束核、最后区、菱形核、中缝苍白核、中缝大核、下橄榄内侧核等。
以上结果证明，经一次条件训练后、单独条件刺激能诱导出一个类似初次抗体应答规律的条件反射性抗体应答增高，从大脑皮质到延髓的多级结构都参与了这一调节过程，它们可能分别在条件训练、条件刺激触发免疫调节等环节起不同作用。; To establish the model of conditioned enhancement of antibody production and explore the neural mechanisms underlying conditioned immunity, this study used a novel taste of saccharin as the conditioned stimulus (CS) and an injection of a protein antigen ovalbumin (OVA) as the unconditioned stimulus (UCS). The CS was paired with UCS only once, and was represented on the day when primary antibody response was attenuated but still expressed strongly. The kinetic changes of conditioned antibody responses were observed afterwards. C-fos immunohistochemistry method was used to map the regional brain activation following the CS representation and during the largest expression of conditioned enhancement of antibody response. The main results are the following:
1. After a CS/UCS pairing was made, reexposure of animals to the CS alone resulted in a sufficiently large enhancement of anti-OVA antibody production that began to be observed at day 15 after the CS representation. The conditioned enhancement of antibody response achieved the peak at day 20, maintained to day 25,
and then attenuated obviously down to baseline.
2. The number of FOS-positive nuclei was significantly higher in OVA immunized rats than that of the non-immunized rats in the areas of anterodorsal thalamic nucleus, central medial nucleus thalamus, paraventricular hypothalamic nucleus, anteroventral preoptic nucleus, Lateral preoptic area, suprachiasmatic nucleus, supraoptic nucleus, basomedial amygdaloid nucleus, basolateral amygdaloid nucleus, lateral amygdaloid nucleus, central amygdaloid nucleus, frontal cortex, periamygdaloid cortex, perirhinal cortex, prepiriform cortex, retrosplenial cortex, and striohypothalamic nucleus.
3. CS/UCS conditionning training significantly increased FOS production in areas of lateral amygdaloid nucleus, medial amygdaloid nucleus, central amygdaloid nucleus, nucleus of lateral olfactory tract, cortical amygdaloid nucleus, basolateral amygdaloid nucleus, bed nucleus of stria terminalis, lateral habenular nucleus, anterodorsal thalamic nucleus, rhomboid nucleus, paraventricular thalamic nucleus, central medial nucleus thalamus, paracentral nucleus, arcuate nucleus, granular insular cortex, dysgranular insular cortex, claustrum, nucleus of diagonal band, retosplenial cortex, cingulum, solitary tract nucleus, medial nucleus of inferior olive, and nucleus raphe pallidus.
4. Higher level of FOS production was found in rats reexposed to the CS alone when compared with the non-reexposed rats in agranular insular cortex, dysgranular insular cortex, granular insular cortex, paraventricular thalamic nucleus, rhomboid nucleus, median eminence, area postrema, nucleus raphe pallidus and solitary tract nucleus.
5. When conditioned antibody production was evident on the day 20 after re-exposure to CS, higher levels of FOS production were detected in conditioned rats than that in the controls in the brain areas including granular insular cortex, solitary tract nucleus, area postrema, rhomboid nucleus, nucleus raphe pallidus, nucleus raphe magnus, and medial nucleus of inferior olive.
In conclusion, the conditioned enhancement of antibody production can be induced by the reexposure of CS alone which was paired with the UCS only once. Many brain regions throughout numerous cortical, limbic, diencephalic and medullary areas are involved in this process. They may play the important roles in the integration of the CS and UCS signals or the CS-evoked regulation of immune response.