【摘要】 近年来研究发现,组蛋白及非组蛋白的乙酰化调节在基因表达及细胞信号转导中起关键作用。休克可引起核心组蛋白及核因子等多种非组蛋白的乙酰化水平下降,而应用组蛋白去乙酰化酶抑制剂(HDACIs)可使下降的乙酰化水平迅速恢复。HDACIs可抑制细胞程序性及非程序性死亡、抑制促炎性因子的释放等,发挥细胞保护作用,从而减轻休克引起的重要器官功能损伤,并显著延长失血性与脓毒症休克动物模型的动物生存时间。其机制包括通过核心组蛋白、非组蛋白的乙酰化调节,增加磷脂酰肌醇3激酶/蛋白激酶B信号转导和阻断Toll样受体4-骨髓样细胞分化因子88-核因子κB信号通路等。更多还原

【Abstract】 Recent studies have shown that acetylation on core histones and key protein play an important role in expression of genes and intracellular signaling. Shock induces deacetylation on histones and nonhistones such as nuclear factor,and administration of histone deacetylase inhibitors( HDACIs) can rapidly reverse the hypoacetylation. HDACIs reduce the injury caused by shock of vital organs,and significantly improve survival in models of lethal hemorrhagic and septic shock through protecting cells from programmed and nonprogrammed cell death and suppressing expression of proinflammatory cytokines. The protective mechanisms are related to acetylation on core histones and nonhistones,and the enhancement of PI3K / Akt signaling and the inhibition of TLR4-MyD88-NFκB signaling pathways.更多还原