Curcumin Alleviates Cerebral Ischemia-reperfusion Injury by Inhibiting NLRP1-dependent Neuronal Pyroptosis
Curcumin Alleviates Cerebral Ischemia-reperfusion Injury by Inhibiting NLRP1-dependent Neuronal Pyroptosis
复制标题
姜黄素通过抑制 NLRP1 依赖性神经元焦亡减轻脑缺血再灌注损伤
DOI：
10.2174/1567202618666210607150140
复制
发表时间：
2021-01-01
影响因子：
2.1
通讯作者：
Zhang, Xin
中科院分区：
文献类型：
--
作者：
Huang, Lifa;Li, Xu;Zhang, Xin
10.2174/1567202618666210607150140摘要：脑缺血再灌注损伤是由缺血脑内的血液再灌注损伤引起的，通常发生在缺血性疾病的治疗阶段，可加重脑组织损伤。目的：姜黄素对神经细胞缺血再灌注损伤有良好的治疗作用，但其作用机制尚不清楚。方法：采用胎鼠大脑皮质神经元缺氧缺糖(OGD)模型和大鼠大脑中动脉闭塞(MCAO)模型，分别在体外和体内模拟脑缺血再灌注损伤。结果：姜黄素对神经细胞增殖有促进作用，对神经元性下垂有抑制作用。此外，我们还发现姜黄素可以改善脑梗塞。Western blotting结果显示，姜黄素可下调OGD和MCAO模型中核苷酸结合的寡聚化结构域蛋白、亮氨酸重复序列和吡咯结构域蛋白1(NLRP1)、半胱氨酸天冬氨酸特异性蛋白1(caspase-1)、Gasdermin D(GSDMD)、IL-1β、IL-6、TNF-α和iNOS蛋白的表达。NLRP1依赖的神经元性下垂在脑缺血再灌注损伤中起重要作用。结论：姜黄素可通过抑制p38MAPK通路，有效抑制NLRP1依赖的神经元性下垂，对脑缺血再灌注损伤具有神经保护作用。
10.2174/1567202618666210607150140 Abstract: Background: Cerebral ischemia-reperfusion injury is caused by a blood reperfusion injury in the ischemic brain and usually occurs in the treatment stage of ischemic disease, which can aggravate brain tissue injury. Objective: Curcumin was reported to exert a good therapeutic effect on neural cells against ischemia-reperfusion injury, However, the mechanism is not clear. Methods: In this study, Oxygen-Glucose Deprivation (OGD) model of fetal rat cerebral cortical neurons and the Middle Cerebral Artery Occlusion (MCAO) model of rats were employed to mimic cerebral ischemia-reperfusion injury in vitro and in vivo, respectively. Results: We confirmed that curcumin has a promotive effect on neuronal proliferation and an inhibitory effect on neuronal pyroptosis. Furthermore, we found that curcumin could improve cerebral infarction. The results of western blotting showed that curcumin down-regulated the expression of nucleotide-binding oligomerization domain-containing protein-, leucine-rich repeats-, and pyrin domain-containing protein 1 (NLRP1), cysteinyl aspartate-specific protease 1 (caspase-1), gasdermin D (GSDMD), IL-1 beta, IL-6, TNF-alpha, and iNOS proteins in OGD and MCAO models. NLRP1-dependent neuronal pyroptosis played an important role in cerebral ischemia-reperfusion injury. Conclusion: Curcumin could effectively inhibit NLRP1-dependent neuronal pyroptosis by suppressing the p38 MAPK pathway and therefore exerted neuroprotective effects against cerebral ischemia-reperfusion injury.