Abstract：
Subarachnoid hemorrhage (SAH) is a neurological condition with high mortality and poor prognosis, and there are currently no effective therapeutic drugs available. Poly (ADP-ribose) polymerase 1 (PARP-1) dependent cell death pathway-parthanatos is closely associated with stroke. We investigated improvements in neurological function, oxidative stress, blood-brain barrier and parthanatos-related protein expression in rats with SAH after intraperitoneal administration of PARP-1 inhibitor (AG14361). Our study found that the expression of parthanatos-related proteins was significantly increased after SAH. Immunofluorescence staining showed increased expression of apoptosis-inducing factor (AIF) in the nucleus after SAH. Administration of PARP-1 inhibitor significantly reduced malondialdehyde (MDA) level and the expression of parthanatos-related proteins. Immunofluorescence staining showed that PARP-1 inhibitor reduced the expression of 8-hydroxy-2\' -deoxyguanosine (8-OHdG) and thus reduced oxidative stress. Moreover, PARP-1 inhibitor could inhibit inflammation-associated proteins level and neuronal apoptosis, protect the blood-brain barrier and significantly improve neurological function after SAH. These results suggest that PARP-1 inhibitor can significantly improve SAH, and the underlying mechanism may be through inhibiting parthanatos pathway.
摘要：
蛛网膜下腔出血(SAH)是一种病死率高、预后差的神经系统疾病。目前尚无有效的治疗药物。聚（ADP-核糖）聚合酶1（PARP-1）依赖性细胞死亡途径-parthanatos与中风密切相关。我们调查了神经功能的改善，氧化应激，腹腔注射PARP-1抑制剂（AG14361）后SAH大鼠血脑屏障和parthanatos相关蛋白的表达。我们的研究发现SAH后parthanatos相关蛋白的表达显着增加。免疫荧光染色显示SAH后细胞核中凋亡诱导因子（AIF）的表达增加。PARP-1抑制剂的施用显著降低了丙二醛(MDA)水平和parthanatos相关蛋白的表达。免疫荧光染色显示PARP-1抑制剂降低了8-羟基-2'-脱氧鸟苷（8-OHdG）的表达，从而降低了氧化应激。此外，PARP-1抑制剂可抑制炎症相关蛋白水平和神经元凋亡,保护血脑屏障，明显改善SAH后神经功能。这些结果表明，PARP-1抑制剂可以显着改善SAH，潜在的机制可能是通过抑制parthanatos途径。
