Intervention Timing and Effect of PJ34 on Astrocytes During Oxygen-glucose Deprivation/reperfusion and Cell Death Pathways

作     者：蔡川 张睿 黄巧英 曹旭 邹良玉 褚晓凡 

作者机构：Department of Neurology Second Clinical College Jinan University Research Centre for Neural Engineering Institute of Biomedical and Health Engineering Shenzhen Institutes of Advanced Technology Chinese Academy of Sciences 

出 版 物：《Journal of Huazhong University of Science and Technology(Medical Sciences)》 (华中科技大学学报（医学英德文版）)

年 卷 期：2015年第35卷第3期

页      面：397-404页

核心收录：

学科分类：0831[工学-生物医学工程（可授工学、理学、医学学位）] 0710[理学-生物学] 1001[医学-基础医学(可授医学、理学学位)] 100101[医学-人体解剖与组织胚胎学] 0805[工学-材料科学与工程（可授工学、理学学位）] 0703[理学-化学] 0836[工学-生物工程] 10[医学] 

基　　金：supported by the National Natural Science Foundation of China(No.30971024) 

主　　题：PARP-1 inhibitor PJ34 primarycortical astrocyte oxygen-glucose deprivation/reperfusion oncosis apoptosis 

摘      要：Poly （ADP-ribose） polymerase-I （PARP-1） plays as a double edged sword in cerebral ischemia-reperfusion, hinging on its effect on the intracellular energy storage and injury severity, and the prognosis has relationship with intervention timing. During ischemia injury, apoptosis and oncosis are the two main cell death pathway sin the ischemic core. The participation of astrocytes in ische- mia-reperfusion induced cell death has triggered more and more attention. Here, we examined the pro- tective effects and intervention timing of the PARP-1 inhibitor PJ34, by using a mixed oxygen-glucose deprivation/reperfusion （OGDR） model of primary rat astrocytes in vitro, which could mimic the ische- mia-reperfusion damage in the ＂ischemic core＂. Meanwhile, cell death pathways of various P J34 treated astrocytes were also investigated. Our results showed that P J34 incubation （10 μmol/L） did not affect release of lactate dehydrogenase （LDH） from astrocytes and cell viability or survival 1 h after OGDR. Interestingly, after 3 or 5 h OGDR, P J34 significantly reduced LDH release and percentage of PI-positive cells and increased cell viability, and simultaneously increased the caspase-dependent apop- totic rate. The intervention timing study demonstrated that an earlier and longer P J34 intervention dur- ing reperfusion was associated with more apparent protective effects. In conclusion, earlier and longer PJ34 intervention provides remarkable protective effects for astrocytes in the ＂ischaemic core＂ mainly by reducing oncosis of the astrocytes, especially following serious OGDR damage.