Chover-Gonzalez A J, Tejedor-Real P, Harbuz M S, Gibert-Rahola J, Larsen P J, Jessop D S
Department of Neurosciences, University of Cadiz, Spain; Division of Medicine, University of Bristol, UK; The Panum Institute, University of Copenhagen, Denmark.
Stress. 1998 Jul;2(3):221-6. doi: 10.3109/10253899809167285.
It has been suggested that glucocorticoid insufficiency consequent to a blunted hypothalamo-pituitary-adrenal (HPA) axis response to stress may be associated with increased susceptibility to certain experimentally induced autoimmune diseases. We have developed a model which allows this hypothesis to be tested within a single population of rats, using the open field stress. Following the open field stress, rats were divided into groups of high or low emotivity on the basis of faecal pellet count. High and low emotivity groups exhibited significantly elevated plasma corticosterone following the open field stress compared to pre-stress levels, but the corticosterone response of the low emotivity rats was significantly lower than that of the high emotivity rats (p < 0.01). Four hours following termination of the stress, groups of high or low emotivity rats were further divided into two groups and given either an intradermal injection of Mycobacterium butyricum or vehicle for the induction of arthritis. Fourteen days after injection of adjuvant, paw volumes in the arthritic high and low emotivity groups were significantly greater than their respective vehicle-injected non-arthritic controls. However, in spite of the differential corticosterone response to stress, there was no significant difference in paw volumes between the arthritic high and low emotivity groups. These data show that an attenuated response to stress is not associated with enhanced susceptibility to the inflammatory disease of adjuvant-induced arthritis, or with increased severity of inflammation as measured by paw volume on day 14. This experimental paradigm can be more widely applied to extend our observations on the relationship between the HPA axis response to stress and susceptibility to inflammation in other models of experimentally induced autoimmune disease.
有人提出，下丘脑 - 垂体 - 肾上腺（HPA）轴对应激反应迟钝导致的糖皮质激素不足，可能与对某些实验性诱导的自身免疫性疾病易感性增加有关。我们开发了一种模型，利用旷场应激，可在单一大鼠群体中对这一假说进行测试。在旷场应激后，根据粪便颗粒计数将大鼠分为高情绪或低情绪组。与应激前水平相比，高情绪组和低情绪组在旷场应激后血浆皮质酮水平显著升高，但低情绪大鼠的皮质酮反应显著低于高情绪大鼠（p < 0.01）。应激结束4小时后，高情绪或低情绪大鼠组再进一步分为两组，分别给予皮内注射丁酸分枝杆菌或赋形剂以诱导关节炎。注射佐剂14天后，关节炎高情绪组和低情绪组的爪体积显著大于各自注射赋形剂的非关节炎对照组。然而，尽管对应激的皮质酮反应存在差异，但关节炎高情绪组和低情绪组之间的爪体积没有显著差异。这些数据表明，对应激的反应减弱与佐剂诱导性关节炎这种炎症性疾病的易感性增加无关，也与第14天通过爪体积测量的炎症严重程度增加无关。这种实验范式可更广泛地应用，以扩展我们对HPA轴对应激反应与实验性诱导的自身免疫性疾病其他模型中炎症易感性之间关系的观察。
