Zahnow C A, Panula P, Yamatodani A, Millhorn D E
Department of Physiology, University of North Carolina, Chapel Hill, North Carolina 27599, USA.
Am J Physiol. 1998 Aug;275(2):L407-13. doi: 10.1152/ajplung.1998.275.2.L407.
Histidine decarboxylase (HDC) is the primary enzyme regulating histamine biosynthesis. Histamine contributes to the pathogenesis of chronic inflammatory disorders such as asthma. Because glucocorticoids are effective in the treatment of asthma, we examined the effects of 6 h of exogenously administered dexamethasone (0.5-3,000 microg/kg ip), corticosterone (0.2-200 mg/kg ip), or endogenously elevated corticosterone (via exposure of rats to 10% oxygen) on HDC expression in the rat lung. HDC transcripts were decreased approximately 73% with dexamethasone treatment, 57% with corticosterone treatment, and 50% with exposure to 10% oxygen. Likewise, HDC enzyme activity was decreased 80% by treatment with dexamethasone and corticosterone and 60% by exposure to 10% oxygen. Adrenalectomy prevented the decreases in HDC mRNA and enzyme activity observed in rats exposed to 10% oxygen, suggesting that the adrenal gland is necessary for the mediation of hypoxic effects on HDC gene expression. These results demonstrate that corticosteroids initiate a process that leads to the decrease of HDC mRNA levels and enzyme activity in rat lung.
组氨酸脱羧酶（HDC）是调节组胺生物合成的主要酶。组胺在诸如哮喘等慢性炎症性疾病的发病机制中起作用。由于糖皮质激素对哮喘治疗有效，我们研究了外源性给予地塞米松（0.5 - 3000微克/千克，腹腔注射）、皮质酮（0.2 - 200毫克/千克，腹腔注射）6小时，或内源性升高皮质酮（通过将大鼠暴露于10%氧气环境）对大鼠肺中HDC表达的影响。地塞米松处理使HDC转录本减少约73%，皮质酮处理使其减少57%，暴露于10%氧气环境使其减少50%。同样，地塞米松和皮质酮处理使HDC酶活性降低80%，暴露于10%氧气环境使其降低60%。肾上腺切除术可防止暴露于10%氧气环境的大鼠出现HDC mRNA和酶活性的降低，这表明肾上腺对于介导低氧对HDC基因表达的影响是必需的。这些结果表明，皮质类固醇启动了一个导致大鼠肺中HDC mRNA水平和酶活性降低的过程。
