基于细胞外组蛋白 HATs/HDACs 平衡调节探讨小青龙汤对脓毒症小鼠急性呼吸窘迫综合征作用机制的研究

组蛋白是存在于细胞核内染色质的重要组成部分，当病原微生物入侵时释放到细胞外，形成细胞外组蛋白(Histone)，可作为反映疾病严重程度的预测因子和可能的治疗靶标，是当前研究热点。在调控基因表达的过程中，组蛋白乙酰化/去乙酰化与肺部疾病密切相关，若表达出现平衡紊乱则导致基因表达失控，造成组织损伤。在脓毒症及ARDS的研究中发现Histone水平均迅速升高，说明ARDS的发生与Histone有着密切联系。因此，Histone可作为分子标靶为ARDS的防治提供新手段。ARDS研究发现，应用去乙酰化酶抑制剂可降低TNF-a水平，减少炎症因子释放，降低ARDS病死率。在ARDS的临床和动物研究方面小青龙汤疗效确切，但目前中药防治ARDS 尚无Histone方面研究。基于上述理论，本研究欲从组蛋白着手，通过研究加味小青龙汤对细胞外组蛋白乙酰化的平衡调节，探讨加味小青龙汤对ARDS的作用机制。

Histone is an important component of chromatin that exists in the nucleus of the cell. When pathogenic microorganisms invade, it is released outside the cell to form extracellular histones (Histone). It can be used as a predictor of the severity of the disease and a possible therapeutic target，which is the current research hotspot. In the process of regulating gene expression, histone acetylation / deacetylation is closely related to lung diseases. If the expression is out of balance, the gene expression will be out of control and cause tissue damage. In the study of sepsis and ARDS, the rapid rise of Histone level was found, which indicates that the occurrence of ARDS is closely related to Histone. Therefore, Histone can be used as a molecular target to provide a new method for the prevention and treatment of ARDS. ARDS research found that the application of deacetylase inhibitors can reduce TNF-a levels, reduce the release of inflammatory factors, and reduce the mortality of ARDS. Xiaoqinglong decoction is effective in clinical and animal research of ARDS, but there is no Histone research on the prevention and treatment of ARDS by Chinese medicine. Based on the above theory, this study intends to start with histones and investigate the effect of Jiawei Xiaoqinglong Decoction on ARDS by studying the balance regulation of extracellular histone acetylation.