糖皮质激素快速抑制人中性粒细胞脱颗粒的非基因组机制

发布时间：2018-06-30 00:03

本文选题：糖皮质激素 + 中性粒细胞　；参考：《第二军医大学》2005年硕士论文

【摘要】：糖皮质激素(glucocorticoids,GCs)是具有重要生理作用及药理作用的甾体激素,对机体的发育、分化以及代谢和免疫调节起着重要作用。临床上GCs广泛用于抗炎和免疫抑制。传统观点认为,GCs是通过基因组机制发挥上述作用的。GCs直接进入靶细胞后,与胞内GCs受体(glucocorticoids receptor,GCR)结合成激素-受体复合物,改变GCR构象使之与热休克蛋白解离,再经过核转位和二聚化,特异地结合于靶基因上的糖皮质激素反应元件(glucocorticoid response elements,GREs)上,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。其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。近十几年来,大量的证据表明,GCs的一些生理学和行为学效应非常快,往往以秒或分钟来计算。从反应时相上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)。通常认为,非基因组作用具有以下特点:(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) 不能被转录/蛋白合成抑制剂所阻断(如转录合成抑制剂放线菌素D,蛋白合成抑制剂放线菌酮);(3) 有些非基因组作用,在GCs与大分子物质(如BSA)偶联后,不能进人细胞内情况下,仍可以发生;(4) 有些非基因组作用可在不能完成mRNA转录和蛋白质合成的细胞或不表达类固醇激素核受体的细胞中观察到;(5) 有些非基因组作用可以不被类固醇激素核受体拮抗剂所阻断。迄今为止,国内外对于GCs的非基因组作用机制研究主要集中在神经内分泌领域,鲜有抗炎和免疫调节作用方面的非基因组机制报道。而GCs在临床上主要用于抗炎和抑制自身免疫。中性粒细胞(neutrophil,又称多形核白细胞,polymorphonuclear leukocyte,PMN)是非常关键的固有免疫细胞,占人外周血白细胞总数的50～70%,处于人体免疫应答第一防线。活化的PMN是一把双面刃,它通过吞噬、脱颗粒、呼吸
[Abstract]:Glucocorticoid (GCs) is a steroid hormone with important physiological and pharmacological effects, which plays an important role in the development, differentiation, metabolism and immune regulation of the body. In clinic, GCs are widely used in anti-inflammatory and immunosuppression. The traditional view is that GCs, which play the role of the above mentioned by the genomic mechanism, directly enter the target cells, and then bind to the intracellular GCs receptor (glucocorticoids receptor) to form a hormone receptor complex, which changes the conformation of the GCs to dissociate them from the heat shock protein (HSPs). After nuclear translocation and dimerization, they are specifically bound to the glucocorticoid response element (glucocorticoid response element GREs, which is located on the target gene. Or acting on nuclear transcription factor AP-1NF- 魏 B and a variety of signal transduction and transcriptional activators (stats) to change the transcription and translation of its downstream related genes. It is characterized by a longer response time, usually more than 30 minutes, up to several hours, days, or more. In the last decade, there has been a great deal of evidence that some physiological and behavioral effects of GCs are very fast, often calculated in seconds or minutes. The rapid effect of GCs is difficult to be explained by genomic interaction in terms of the phase and molecular basis of the reaction. It has been proved that GCs have a fast nongenomic interaction (nongenomic effects). Which is different from genomic interaction. It is generally believed that nongenomic interactions have the following characteristics: (1) they act fast (seconds to minutes) and recover quickly (after the hormone is removed, The rapid disappearance of); (2 could not be blocked by transcriptional / protein synthesis inhibitors (such as transcriptional synthesis inhibitor actinomycin D, protein synthesis inhibitor actinomycin); (3). If you can't get inside a human cell, (4) some non-genomic interactions can be observed in cells that cannot complete mRNA transcription and protein synthesis or in cells that do not express steroid hormone nuclear receptors; (5) some non-genomic effects can be avoided by steroid hormone nuclei. Blocked by receptor antagonists. Up to now, the studies on the mechanism of non-genomic action of GCs are mainly focused on the neuroendocrine field, and there are few reports on the non-genomic mechanisms of anti-inflammatory and immunomodulatory effects at home and abroad. GCs are mainly used for anti-inflammatory and anti-autoimmune in clinic. Neutrophiles, also known as polymorphonuclear leukocyte (PMN), are the key innate immune cells, accounting for 50% 70% of the total number of human peripheral blood leukocytes, and are in the first line of human immune response. Activated PMN is a double-sided blade that is swallowed, degranulated, and breathed.
【学位授予单位】：第二军医大学
【学位级别】：硕士
【学位授予年份】：2005
【分类号】：R341

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