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糖皮质激素是胸腺儿茶酚胺能系统的主要调节因子?

Glucocorticoids, master modulators of the thymic catecholaminergic system?

机构信息

Immunology Research Centre "Branislav Janković", Institute of Virology, Vaccines and Sera "Torlak", Belgrade, Serbia.

出版信息

Braz J Med Biol Res. 2010 Mar;43(3):279-84. doi: 10.1590/s0100-879x2010007500005.

DOI:10.1590/s0100-879x2010007500005
PMID:20401436
Abstract

There is evidence that the major mediators of stress, i.e., catecholamines and glucocorticoids, play an important role in modulating thymopoiesis and consequently immune responses. Furthermore, there are data suggesting that glucocorticoids influence catecholamine action. Therefore, to assess the putative relevance of glucocorticoid-catecholamine interplay in the modulation of thymopoiesis we analyzed thymocyte differentiation/maturation in non-adrenalectomized and andrenalectomized rats subjected to treatment with propranolol (0.4 mg.100 g body weight-1.day-1) for 4 days. The effects of beta-adrenoceptor blockade on thymopoiesis in non-adrenalectomized rats differed not only quantitatively but also qualitatively from those in adrenalectomized rats. In adrenalectomized rats, besides a more efficient thymopoiesis [judged by a more pronounced increase in the relative proportion of the most mature single-positive TCRalphabetahigh thymocytes as revealed by two-way ANOVA; for CD4+CD8- F (1,20) = 10.92, P < 0.01; for CD4-CD8+ F (1,20) = 7.47, P < 0.05], a skewed thymocyte maturation towards the CD4-CD8+ phenotype, and consequently a diminished CD4+CD8-/CD4-CD8+ mature TCRalphabetahigh thymocyte ratio (3.41 +/- 0.21 in non-adrenalectomized rats vs 2.90 +/- 0.31 in adrenalectomized rats, P < 0.05) were found. Therefore, we assumed that catecholaminergic modulation of thymopoiesis exhibits a substantial degree of glucocorticoid-dependent plasticity. Given that glucocorticoids, apart from catecholamine synthesis, influence adrenoceptor expression, we also hypothesized that the lack of adrenal glucocorticoids affected not only beta-adrenoceptor- but also alpha-adrenoceptor-mediated modulation of thymopoiesis.

摘要

有证据表明,应激的主要介质,即儿茶酚胺和糖皮质激素,在调节胸腺生成和免疫反应方面发挥着重要作用。此外,有数据表明糖皮质激素影响儿茶酚胺的作用。因此,为了评估糖皮质激素-儿茶酚胺相互作用在调节胸腺生成中的潜在相关性,我们分析了未行肾上腺切除术和行肾上腺切除术大鼠在接受普萘洛尔(0.4mg.100g 体重-1.天-1)治疗 4 天后的胸腺细胞分化/成熟情况。β-肾上腺素受体阻断对未行肾上腺切除术大鼠的胸腺生成的影响不仅在数量上,而且在性质上也与行肾上腺切除术大鼠不同。在行肾上腺切除术大鼠中,除了更有效的胸腺生成[通过双向 ANOVA 更明显地增加最成熟的单阳性 TCRalphabetahigh 胸腺细胞的相对比例来判断;对于 CD4+CD8-,F(1,20)=10.92,P<0.01;对于 CD4-CD8+,F(1,20)=7.47,P<0.05],还发现了向 CD4-CD8+表型的偏倚的胸腺细胞成熟,以及随之而来的 CD4+CD8-/CD4-CD8+成熟 TCRalphabetahigh 胸腺细胞比率降低(未行肾上腺切除术大鼠为 3.41+/-0.21,行肾上腺切除术大鼠为 2.90+/-0.31,P<0.05)。因此,我们假设儿茶酚胺对胸腺生成的调节表现出很大程度的糖皮质激素依赖性可塑性。鉴于糖皮质激素除了儿茶酚胺合成外,还影响肾上腺素受体表达,我们还假设缺乏肾上腺糖皮质激素不仅影响β-肾上腺素受体,而且影响α-肾上腺素受体对胸腺生成的调节。

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