CAJ | 학술논문

慢性阻塞性肺疾病(chronic obstructive pulmonary disease,COPD)是一种以气流受限为特征的气道高反应性疾病，气流受限不完全可逆，呈进行性发展，与肺部对有害气体或有害颗粒的异常炎症反应有关，吸烟是COPD的主要危险因素。糖皮质激素作为治疗炎症性疾病的主要药物，它能增强抗炎基因的表达和减少炎症基因的转录，从而抑制炎症反应过程中的多个环节。但是糖皮质激素在COPD的治疗中对炎症效应细胞、细胞因子、蛋白酶等无抑制作用，相反，还延长了中性粒细胞的生存时间，这一现象被称为糖皮质激素抵抗。组蛋白去乙酰化酶（HDAC）是一种重要的调节基因表达的核酶家族，主要作用是调节炎症相关基因的表达，而HAT和HDAC的动态平衡对炎症基因的转录活性和炎症反应程度的调节起关键作用。国内外学者对COPD、HDAC和糖皮质激素抵抗的相关关系作了大量研究，证明了糖皮质激素在一定程度上通过HDAC发挥其抗炎作用，而吸烟等因素引起的HDAC活性降低可能参与了糖皮质激素抵抗的形成。COPD中的糖皮质激素抵抗，其产生的主要原因是氧化应激反应干扰了GR核移位，阻断了糖皮质激素-GR复合物与DNA的结合，从而限制了其炎症拮抗效应的发挥。而氨茶碱、N—乙酰半胱氨酸、布地奈德等能够活化HDAC，拮抗因HDAC表达降低而引起的糖皮质激素抵抗，为COPD的治疗寻找新的路径。但氧化应激是怎样作用于HDAC引起表达下调、HDAC/HAT失衡在COPD中的影响、各种炎症因子在HDAC/HAT失衡和糖皮质激素抵抗中扮演何种角色等问题，仍有待于进一步研究。
만성조새성폐질병(chronic obstructive pulmonary disease,COPD)시일충이기류수한위특정적기도고반응성질병，기류수한불완전가역，정진행성발전，여폐부대유해기체혹유해과립적이상염증반응유관，흡연시COPD적주요위험인소。당피질격소작위치료염증성질병적주요약물，타능증강항염기인적표체화감소염증기인적전록，종이억제염증반응과정중적다개배절。단시당피질격소재COPD적치료중대염증효응세포、세포인자、단백매등무억제작용，상반，환연장료중성립세포적생존시간，저일현상피칭위당피질격소저항。조단백거을선화매（HDAC）시일충중요적조절기인표체적핵매가족，주요작용시조절염증상관기인적표체，이HAT화HDAC적동태평형대염증기인적전록활성화염증반응정도적조절기관건작용。국내외학자대COPD、HDAC화당피질격소저항적상관관계작료대량연구，증명료당피질격소재일정정도상통과HDAC발휘기항염작용，이흡연등인소인기적HDAC활성강저가능삼여료당피질격소저항적형성。COPD중적당피질격소저항，기산생적주요원인시양화응격반응간우료GR핵이위，조단료당피질격소-GR복합물여DNA적결합，종이한제료기염증길항효응적발휘。이안다감、N—을선반광안산、포지내덕등능구활화HDAC，길항인HDAC표체강저이인기적당피질격소저항，위COPD적치료심조신적로경。단양화응격시즘양작용우HDAC인기표체하조、HDAC/HAT실형재COPD중적영향、각충염증인자재HDAC/HAT실형화당피질격소저항중분연하충각색등문제，잉유대우진일보연구。
Chronic Obstructive Pulmonary Disease(COPD)is a restricted flow characteristics of airway hyperresponsiveness disease that airflow limitation that is not fully reversible and progressive development. Related with lung abnormal inflammatory response to noxious particles or gases.Smoking is a major risk factor for COPD.Glucocorticoid is the main drug for the treatment of inflammatory diseases,it can enhance the expression of anti-inflammatory gene and reduced inflammatory gene transcription and inhibiting the inflammatory reaction.But corticosteroids did not inhibit cell factor,inflammatory effector cells,protease of COPD,On the contrary prolong neutrophil survival time,and this phenomenon is known as glucocorticoid resistance.Histone deacetylase(HDAC) is an important regulator of gene expression of the ribozyme family, the main role is to regulate the expression of genes related to inflammation.Dynamic balance of HAT and HDAC on the inflammatory gene transcription activity and the degree of inflammatory reaction plays a key role.Domestic and foreign scholars have made a lot of researches on the relationship between COPD, HDAC and glucocorticoid resistance that glucocorticoids exerts its anti-inflammatory effect by HDAC,and smoking causes the decrease of HDAC activity may be involved in the formation of glucocorticoid resistance.COPD of glucocorticoid resistance is due to oxidative stress interferes with the nuclear translocation of GR and prevented glucocorticoids combined with -GR complex and DNA,so the anti-inflammatory effect is limited.In order to find a new path for the treatment of COPD,The study found aminophylline, N acetyl cysteine, budesonide can activate HDAC and decrease expression of HDAC cause by glucocorticoid resistance.The need for further research what is the role of oxidative stress in HDAC caused down-regulation,effect of HDAC/HAT imbalance in COPD and various inflammatory factors play a role in HDAC/HAT imbalance and glucocorticoid resistance etc.