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染色体核心组蛋白分子作为各种炎症因子和炎症信号转导的关键性终端蛋白质分子,具有基因转录“开关”分子的功能,其活性受组蛋白转乙酰酶/脱乙酰酶(HAT/HDAC)的调节。HAT活性增高,组蛋白分子过乙酰化,DNA表现为解链效应,促进基因转录;而HDAC活性增高则出现相反的效应,基因转录变沉默。HAT和HDAC的动态平衡对基因的转录活性和炎症反应程度的调节起关键作用。慢性阻塞性肺疾病(COPD)肺部氧化应激反应的持续存在,明显降低了肺组织HDAC酶的活性,组蛋白乙酰化/去乙酰化平衡被打破,组蛋白分子过乙酰化、炎症蛋白基因的转录和炎症蛋白的合成得到加强,阻断了糖皮质激素的抗炎症反应效应。小剂量氨茶碱恢复COPD肺组织HDAC活性,减少炎症介质和细胞因子合成和释放,能够改善气道炎症对糖皮质激素治疗的反应性。
As a key terminal protein molecule of various inflammatory factors and inflammatory signal transduction, the chromosomal core histone molecule has the function of gene transcriptional “switch” molecule and its activity is regulated by histone acetyltransferase / deacetylase (HAT / HDAC) adjust. Increased HAT activity, histone acetyltransferase, DNA showed a melting effect, and promote gene transcription; HDAC activity increased the opposite effect, gene transcription becomes silent. The homeostasis of HAT and HDAC plays a key role in the regulation of gene transcriptional activity and the degree of inflammatory response. The persistence of oxidative stress in the lungs of chronic obstructive pulmonary disease (COPD) significantly reduces HDAC enzyme activity in the lung tissue, the balance of histone acetylation / deacetylation is broken, histone acetylcholinesterase, inflammatory protein genes The transcription and synthesis of inflammatory proteins are enhanced, blocking the glucocorticoid anti-inflammatory response. Low-dose aminophylline restores HDAC activity in COPD lung tissue, reduces the synthesis and release of inflammatory mediators and cytokines, and improves the responsiveness of airway inflammation to glucocorticoid therapy.