中文摘要：

目的探讨组蛋白去乙酰化酶抑制剂曲古抑菌素A（trichostatinA，TSA）对人神经母细胞瘤细胞（SH—SY5Y）缺氧／缺糖（oxygen—gh,eosedeprjration，OGD）损伤的保护作用及其可能机制。方法采用化学方法建立SH—SY5Y细胞不同时间（1、2、4、6和8h）持续性OGD损伤模型，MTr法检测细胞活性，以评估持续性OGD损伤对SH—SY5Y细胞的损伤程度。继而观察TSA（10、20、40、80nmol·L^-1）对OGD诱导的神经元损伤的影响，实验指标如下：倒置显微镜观察细胞形态学变化，MTT检测TSA对细胞活性的影响，Propidiumiodide（PI）和Hoechst33258染色检测细胞凋亡与坏死情况，荧光显微镜检测各组细胞内活性氧（reactiveoxygenspecies，ROS）含量和线粒体膜电位（mitochondrionmembranepoten—tial，MMP）的变化。结果OGD损伤2h，模型组的细胞活性和MMP水平较对照组明显降低，并随OGD时间的延长而变化越明显。而ROS含量较对照组明显升高，Hoechst和PI双染检测也发现染色质凝聚，核碎裂，凋亡小体产生，并随OGD时间的延长，凋亡和坏死细胞的数量增加。与模型组相比，40nmol·L^-1 TSA能明显提高OGD诱导的神经元的活性，降低细胞内ROS含量，以及提高MMP水平。结论TSA对OGD诱导SH—SY5Y细胞缺氧／缺糖损伤具有明显的保护作用，其保护机制可能与降低细胞内ROS水平及维持MMP的高能状态有关。

英文摘要：

Aim To investigate the protective effects of histone deacetylase inhibitor （HDACi） , trichostatin A （ TSA）, on oxygen-glucose deprivation （OGD） in SH-SYSY cells and the underlying mechanism. Meth- ods SH-SYSY cells were cultured with DMEM medi- um, OGD model was established and evaluated based on cell viability. Afterwards, the influences of TSA （10, 20, 40 and 80 nmol·L^-1） treatment on the neuron injury induced by OGD were analyzed, morpho- logical changes were observed with inverted micro- scope, cell viability was measured by methyl thiazolyl tetrazolium （MTT） assay, cell apoptosis and necrosis were detected by PI and Hoechst staining, the level of intracellular reactive oxygen species （ROS） and poten- tial of mitochondfial membrane （MMP） were evaluated by Fluorescence microscope. Results Oxygen-glucose deprivation for 2 hours significantly suppressed the cell viability and MMP of SH-SY5Y, the intracellular level of ROS increased obviously. Moreover, the number of apoptotic and necrotic cells increased as the extending of oxygen-glucose deprivation. Compared with OGD group, 40 nmol·L^-1 TSA significantly improved cel- lular viability and MMP, reduced intracellular ROS. Conclusion These data demonstrate the neuroprotec- tire effects of TSA on OGD induced injury in SH-SY5Y cells, the underlying mechanisms may partially be due to the effects of TSA on an anti-oxidative stress, and maintaining of mitochondria function.