抑制HDAC9-MEF2相互作用可通过上调cGMP依赖性激酶Ⅱ表达抑制缺血性脑卒中后的神经元凋亡
Chinese Journal of Pharmacology and Toxicology（2023）
Abstract
目的 全基因组关联研究发现组蛋白去乙酰化酶9(HDAC9)与缺血性脑卒中相关.因此需要研究HDAC9在缺血性脑卒中中的作用与机制.方法 在野生型(WT)小鼠和神经元缺失HDAC9(HDAC9 cKO)的小鼠上,利用脑中动脉栓塞再灌注(tMCAO)模型模拟缺血性脑卒中脑损伤.通过TTC检测脑损伤,利用免疫荧光组化、Western印迹法、蛋白免疫共沉淀、染色质免疫共沉淀和荧光定量PCR检测HDAC9在缺血性脑卒中的作用和机制.结果 HDAC9 cKO小鼠与WT小鼠相比,半暗带中神经元凋亡及脑梗死体积显著降低的同时cGMP依赖性激酶Ⅱ(cGKⅡ)表达上调,抑制cGKⅡ表达后能够逆转上述现象.进一步研究发现,HDAC9通过与MEF2相互作用抑制tMCAO后cGKⅡ表达.利用BML210抑制HDAC9与MEF2的相互作用能够显著降低脑梗死体积.结论 抑制MEF2与HDAC9相互作用能够上调cGKⅡ表达,进而抑制缺血性脑卒中后神经元凋亡,降低脑损伤.
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