Miller Gregory E, Chen Edith
Department of Psychology, University of British Columbia, 2136 West Mall, Vancouver, BC, Canada V6T 1Z4.
Proc Natl Acad Sci U S A. 2006 Apr 4;103(14):5496-501. doi: 10.1073/pnas.0506312103. Epub 2006 Mar 27.
Despite evidence that stressful experience can exacerbate the symptoms of asthma, little is known about the biological mechanisms through which this occurs. This study examined whether life stress reduces expression of the genes coding for the glucocorticoid receptor and the beta(2)-adrenergic receptor. A total of 77 children were enrolled in the study (59% male; mean age, 13.5 years). Thirty-nine of them were physician-diagnosed with asthma, and 38 were healthy. After an in-depth interview regarding stressful experiences, leukocytes were collected through antecubital venipuncture, and real-time RT-PCR was used to quantify mRNA. Chronic stress was associated with reduced expression of mRNA for the beta(2)-adrenergic receptor among children with asthma. In the sample of healthy children, however, the direction of this effect was reversed. The occurrence of a major life event in the 6 months before the study was not sufficient to influence patterns of gene expression. When such events occurred in the context of a chronic stressor, however, their association with patterns of gene expression was accentuated. Children with asthma who simultaneously experienced acute and chronic stress exhibited a 5.5-fold reduction in glucocorticoid receptor mRNA and a 9.5-fold reduction in beta(2)-adrenergic receptor mRNA relative to children with asthma without comparable stressor exposure. These findings suggest that stressful experience diminishes expression of the glucocorticoid and beta(2)-adrenergic receptor genes in children with asthma. To the extent that it diminishes sensitivity to the antiinflammatory properties of glucocorticoids or the bronchodilatory properties of beta-agonists, this process could explain the increased asthma morbidity associated with stress.
尽管有证据表明压力经历会加剧哮喘症状，但对于其发生的生物学机制却知之甚少。本研究调查了生活压力是否会降低编码糖皮质激素受体和β₂ - 肾上腺素能受体的基因表达。共有77名儿童参与了该研究（59%为男性；平均年龄13.5岁）。其中39名儿童被医生诊断为哮喘，38名儿童健康。在深入访谈压力经历后，通过肘前静脉穿刺采集白细胞，并使用实时RT-PCR定量mRNA。慢性压力与哮喘儿童中β₂ - 肾上腺素能受体的mRNA表达降低有关。然而，在健康儿童样本中，这种影响的方向相反。研究前6个月内发生重大生活事件不足以影响基因表达模式。然而，当这些事件在慢性应激源的背景下发生时，它们与基因表达模式的关联会增强。与没有类似应激源暴露的哮喘儿童相比，同时经历急性和慢性压力的哮喘儿童糖皮质激素受体mRNA降低了5.5倍，β₂ - 肾上腺素能受体mRNA降低了9.5倍。这些发现表明，压力经历会降低哮喘儿童中糖皮质激素和β₂ - 肾上腺素能受体基因的表达。就其降低对糖皮质激素抗炎特性或β - 激动剂支气管扩张特性的敏感性而言，这一过程可以解释与压力相关的哮喘发病率增加的原因。
