本文選題：糖皮質(zhì)激素 + 中性粒細(xì)胞　； 參考：《第二軍醫(yī)大學(xué)》2005年碩士論文

【摘要】：糖皮質(zhì)激素(glucocorticoids,GCs)是具有重要生理作用及藥理作用的甾體激素,對(duì)機(jī)體的發(fā)育、分化以及代謝和免疫調(diào)節(jié)起著重要作用。臨床上GCs廣泛用于抗炎和免疫抑制。 傳統(tǒng)觀點(diǎn)認(rèn)為,GCs是通過基因組機(jī)制發(fā)揮上述作用的。GCs直接進(jìn)入靶細(xì)胞后,與胞內(nèi)GCs受體(glucocorticoids receptor,GCR)結(jié)合成激素-受體復(fù)合物,改變GCR構(gòu)象使之與熱休克蛋白解離,再經(jīng)過核轉(zhuǎn)位和二聚化,特異地結(jié)合于靶基因上的糖皮質(zhì)激素反應(yīng)元件(glucocorticoid response elements,GREs)上,或者作用于核轉(zhuǎn)錄因子AP-1、NF-κB及多種信號(hào)轉(zhuǎn)導(dǎo)與轉(zhuǎn)錄活化因子(STATs),改變其下游相關(guān)基因的轉(zhuǎn)錄及翻譯。其特點(diǎn)是應(yīng)答時(shí)間較長(zhǎng),通常在三十分鐘以上,長(zhǎng)的可達(dá)數(shù)小時(shí)、數(shù)日,甚至更長(zhǎng)。 近十幾年來,大量的證據(jù)表明,GCs的一些生理學(xué)和行為學(xué)效應(yīng)非�？�,往往以秒或分鐘來計(jì)算。從反應(yīng)時(shí)相上以及反應(yīng)的分子基礎(chǔ)來看,GCs的這種快速效應(yīng)難以用基因組作用解釋�，F(xiàn)已證明,GCs存在不同于基因組作用的快速非基因組作用(nongenomic effects)。 通常認(rèn)為,非基因組作用具有以下特點(diǎn):(1) 作用快(數(shù)秒到數(shù)分鐘),恢復(fù)快(去除激素后,作用快速消失);(2) 不能被轉(zhuǎn)錄/蛋白合成抑制劑所阻斷(如轉(zhuǎn)錄合成抑制劑放線菌素D,蛋白合成抑制劑放線菌酮);(3) 有些非基因組作用,在GCs與大分子物質(zhì)(如BSA)偶聯(lián)后,不能進(jìn)人細(xì)胞內(nèi)情況下,仍可以發(fā)生;(4) 有些非基因組作用可在不能完成mRNA轉(zhuǎn)錄和蛋白質(zhì)合成的細(xì)胞或不表達(dá)類固醇激素核受體的細(xì)胞中觀察到;(5) 有些非基因組作用可以不被類固醇激素核受體拮抗劑所阻斷。 迄今為止,國(guó)內(nèi)外對(duì)于GCs的非基因組作用機(jī)制研究主要集中在神經(jīng)內(nèi)分泌領(lǐng)域,鮮有抗炎和免疫調(diào)節(jié)作用方面的非基因組機(jī)制報(bào)道。而GCs在臨床上主要用于抗炎和抑制自身免疫。 中性粒細(xì)胞(neutrophil,又稱多形核白細(xì)胞,polymorphonuclear leukocyte,PMN)是非常關(guān)鍵的固有免疫細(xì)胞,占人外周血白細(xì)胞總數(shù)的50～70%,處于人體免疫應(yīng)答第一防線�；罨腜MN是一把雙面刃,它通過吞噬、脫顆粒、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.
【學(xué)位授予單位】：第二軍醫(yī)大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2005
【分類號(hào)】：R341

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