小鼠生命早期受到心理应激后通过下丘脑-垂体-肾上腺轴的作用加重成年后哮喘发作
2007/06/27
许多证据表明心理应激在短期内可加重哮喘发作，但对于儿童时期接受的应激是否对成年后的哮喘有影响还知之甚少。Chida Y 等在小鼠身上进行了这方面的研究。他们采用一个通讯箱，在小鼠四周龄时给予3次心理或生理刺激，而后在第八和十周给予抗原致敏，第十一周时给予抗原激发。结果发现抗原激发后24小时，接受心理或生理应激的小鼠与未接受应激的对照组相比，无论总的单核细胞数和嗜酸性粒细胞数还是气道反应性均增高，而血清IgE抗体水平无差异。同时发现，受到心理应激的小鼠在抗原激发后体内皮质激素水平的增加较对照组明显减少，生理应激组小鼠与对照组无明显差异。如果在抗原激发前给予皮质激素受体拮抗剂RU-486可完全抑制心理应激所致的哮喘的加重。而如果事先予神经激肽-1受体拮抗机GR-82334预处理则不能逆转生理应激所致的哮喘气道炎症的加重。因此，作者认为早期受到心理应激通过下丘脑-垂体-肾上腺轴的低反应性使后期哮喘加重，而生理应激则通过下丘脑-垂体-肾上腺轴和神经激肽-1受体以外的机制使哮喘加重。
（王苹莉 浙江大学医学院附属二院呼吸内科 310008 摘译）
(Am J Respir Care Med.2007;175:316-322)
Early-life psychological stress exacerbates adult mouse asthma via the hypothalamus-pituitary-adrenal axis.
Chida Y, Sudo N, Sonda J, Hiramoto T, Kubo C.
RATIONALE: Despite accumulating evidence that psychological stress has a short-lasting detrimental effect on asthma, little is known about the way stress in childhood predisposes to adult asthma.
OBJECTIVES: Using a communication box, we investigated the long-lasting effect of early psychological and physical stress on adult asthma in mice.
METHODS: Male BALB/c mice were exposed to either psychological stress or physical stress three times (every other day) during their fourth week of life. The mice were sensitized to ovalbumin at 8 and 10 weeks, and an ovalbumin airway challenge was conducted at the age of 11 weeks.
RESULTS: Twenty-four hours after ovalbumin challenge, both psychological and physical stress-exposed mice exhibited a significant acceleration in the number of total mononuclear cells and eosinophils and airway hyperresponsiveness compared with control mice. No differences in serum anti-OVA-specific immunoglobulin E levels were found between stress-exposed and control animals after antigen sensitization. In the psychological stress group, but not in the physical stress group, an elevation of the serum corticosterone levels during ovalbumin challenge was significantly attenuated in comparison with the control group. Moreover, pretreatment with RU-486, a glucocorticoid receptor antagonist, before ovalbumin challenge completely inhibited a psychological stress-induced exacerbation of asthma. However, pretreatment with GR-82334, a neurokinin-1 receptor antagonist, failed to affect physical stress-induced augmentation of airway inflammation.
CONCLUSION: Early psychological and physical stresses aggravated adult asthma via hyporesponsiveness of the hypothalamic-pituitary-adrenal axis during antigen challenge and via a pathway(s) distinct from the hypothalamic-pituitary-adrenal axis or neurokinin-1 receptors.
（Am J Respir Crit Med. 2007 Feb 15;175(4):316-22）
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抗原激发后的哮喘气道高反应性与气道重塑相关而非持续气道炎症
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IL4受体α突变与哮喘发作及肥大细胞数量IgE表达相关
