糖皮质激素快速抑制气道平滑肌收缩的非基因组机制

发布时间：2018-08-04 21:43

【摘要】：糖皮质激素(glucocorticoids,GCs)在体内是由肾上腺皮质束状带合成和分泌的一类甾体激素,具有重要生理作用及药理作用,对机体发育、分化以及代谢和免疫调节等起着重要作用。临床上GCs广泛用于抗炎和免疫抑制。传统观点认为,GCs通过基因组机制发挥上述作用。GCs进入靶细胞后,与胞内GCs受体(glucocorticoids receptor,GCR)结合形成激素-受体复合物,GCR构象随之改变并与热休克蛋白解离,再经过核转位和二聚化,与靶基因上的糖皮质激素反应元件(glucocorticoid response elements,GREs)特异性地结合,或者作用于核转录因子AP-1、NF-_κB及多种信号转导与转录活化因子(STATs),改变其下游相关基因的转录及翻译。基因组机制特点是应答时间较长,通常在三十分钟以上,长的可达数小时、数日甚至更长。另一方面,大量的证据表明,除典型的基因组机制以外,GCs能够引起许多发生非常快速的生理学和行为学效应,只需要数秒或数分钟就能发生。从反应时相以及反应的分子基础来看,GCs的这种快速效应难以用基因组作用解释。现已证明,GCs存在不同于基因组作用的快速非基因组作用(nongenomic effects)。与基因组机制相比,这种效应有以下特点:(1)作用快(数秒到数分钟),恢复快(去除激素后,作用快速消失);(2)有些非基因组作用不能被类固醇激素核受体拮抗剂(舅如RU486)所阻断,也不能被转录或蛋白合成抑制剂(如转录合成抑制剂放线菌素D,蛋白合成抑制剂放线菌酮)所阻断;(3)有些非基
[Abstract]:Glucocorticoid hormone (GCs) is a steroid hormone synthesized and secreted by the adrenal cortical bundles in vivo. It has important physiological and pharmacological effects and plays an important role in the development differentiation metabolism and immune regulation of the body. GCs is widely used in anti-inflammatory and immunosuppression. The traditional view is that GCs play the above role through genomic mechanism. GCs enter into the target cells, and form the conformation of hormone receptor complex (GCR) by binding to glucocorticoids receptor (glucocorticoids receptor). The conformation changes and dissociates from heat shock protein (HSPs), and then goes through nuclear translocation and dimerization. Binding specifically to the glucocorticoid response element (glucocorticoid response element GREs on the target gene, or acting on the transcription factor AP-1, NF-kappa B and a variety of signal transduction and transcriptional activator (STATs), altered the transcription and translation of its downstream genes. Genomic mechanisms are characterized by longer response times, usually more than 30 minutes, up to several hours, days or more. On the other hand, there is considerable evidence that GCs can cause many physiological and behavioral effects that occur very quickly, in seconds or minutes, in addition to typical genomic mechanisms. The rapid effect of GCs is difficult to be explained by genomic interaction from the point of view of the reaction phase and the molecular basis of the reaction. It has been proved that GCs have a fast nongenomic interaction (nongenomic effects). Which is different from genomic interaction. Compared with the genomic mechanism, this effect has the following characteristics: (1) it acts faster (seconds to minutes) and recovers quickly (after the hormone is removed, the effect rapidly disappears); (2) some non-genomic effects cannot be blocked by steroid hormone nuclear receptor antagonists (uncle such as RU486). Also can not be blocked by transcription or protein synthesis inhibitors (such as transcriptional synthesis inhibitor actinomycin D, protein synthesis inhibitor actinomycin); (3) some non-groups
【学位授予单位】：第二军医大学
【学位级别】：硕士
【学位授予年份】：2006
【分类号】：R332;R96

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