PARP-1对缺血性脑炎症反应调控的性别差异性及其机制

缺血性卒中是一种性别差异性较大的疾病，针对性别差异性的治疗策略及其机制研究越来越受到重视。脑缺血后，炎症反应贯穿整个脑损伤的病理过程，与卒中的高致死率、高致残率密切相关。我们前期研究发现，多聚(腺苷二磷酸-核糖)聚合酶[Poly(ADP-ribose)polymerase, PARP]-1抑制剂在体内可减轻雄性大鼠卒中后的炎症反应和神经元死亡，并可促进神经元再生；在体外可抑制LPS或TNF-α诱导的小胶质细胞活化和炎症介质释放。此外，最新研究发现PARP-1抑制剂在缺血性脑卒中的神经保护作用具有性别差异性，机制不清。本课题将分别制备体内外不同性别的脑缺血模型，进一步研究PARP-1调控脑卒中后炎症反应作用的性别差异性及其相关机制，为开拓以缺血性脑卒中后炎症反应为靶向的性别差异性治疗策略提供理论基础。

Acute ischemic stroke is a sexually dimorphic disease. Recently, many experimental and clinical studies shift their attention to explore gender-based therapeutic strategies and relevant mechanisms. Inflammation is involved in almost whole process of stroke pathology, therefore serves as a key determinant for high morbidity and mortality in ischemic stroke. Our previous in vivo studies showed that the Poly (ADP-ribose) polymerase-1 (PARP-1) inhibitor could alleviate post-stroke inflammation and neuronal death, and promote later neurogenesis in male rats. Furthermore, in vitro PARP-1 inhibitor could reduce LPS or TNF-α induced microglial activation and inflammatory factors release. In addition, recent evidence suggests that PARP-1 inhibitor exerts neuroprotection in males but not females after stroke. The underlying mechanisms for this gender difference are not fully identified. Hence, using both male and female stroke models, we will further investigate roles of PARP-1 in post-stroke inflammation, and the impact of gender difference and underlying mechanisms. This research aims to explore evidence for post-stroke inflammation targeted and gender-based therapeutic strategies for stroke treatment.