组蛋白去乙酰化酶抑制剂在脓毒症及急性肺损伤中的作用研究进展

Research Progress in Role of Histone Deacetylase Inhibitors in Treatment of Sepsis and Acute Lung Injury

组蛋白去乙酰化酶抑制剂(HADCIs)具有干扰组蛋白去乙酰化酶的功能,可通过提高细胞内组蛋白的乙酰化程度,调控基因转录,在恶性肿瘤的治疗中发挥重要作用。在脓毒症及其相关肺损伤中,HDACIs可发挥抑制炎症反应以及组织器官保护等多重作用,组蛋白乙酰化调控可能成为有价值的脓毒症治疗靶点,其机制包括抑制Toll样受体4-髓样细胞分化因子88-核因子κB/促分裂原活化的蛋白激酶信号通道,下调炎症相关因子释放;通过调控微RNA转录水平抑制炎症相关基因表达;抑制肺泡上皮细胞凋亡等。

Histone deacetylase inhibitors(HDACIs)can interfere with the function of histone deacetylase.They play an important role in the treatment of malignant tumors by increasing the degree of acetylation of histone and regulating gene transcription.HDACIs can play multiple roles in sepsis and related lung injury,such as inhibiting inflammation and protecting tissues and organs.Histone acetylation regulation may become a valuable target for sepsis treatment.The protective mechanism may include inhibiting Toll-like receptor 4-myeloid differentiation factor 88-nuclear factorκB/mitogen activated protein kinase signaling pathway to down-regulate the release of pro-inflammatory cytokines,inhibition of inflammation related gene expression by regulation of microRNA transcription level,and attenuating lung tissue cell apoptosis.