Department of Neurosurgery, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310006, China.
First Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310053, China.
Curr Neurovasc Res. 2021;18(2):189-196. doi: 10.2174/1567202618666210607150140.
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.
Curcumin was reported to exert a good therapeutic effect on neural cells against ischemia- reperfusion injury, However, the mechanism is not clear.
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.
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-1β, IL-6, TNF-α, and iNOS proteins in OGD and MCAO models. NLRP1- dependent neuronal pyroptosis played an important role in cerebral ischemia-reperfusion injury.
Curcumin could effectively inhibit NLRP1-dependent neuronal pyroptosis by suppressing the p38 MAPK pathway and therefore exerted neuroprotective effects against cerebral ischemia- reperfusion injury.
脑缺血再灌注损伤是由缺血性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。
姜黄素对缺血再灌注损伤的神经细胞有较好的治疗作用，但作用机制尚不清楚。
本研究采用胎鼠大脑皮质神经元氧葡萄糖剥夺（OGD）模型和大鼠大脑中动脉闭塞（MCAO）模型，分别模拟体外和体内脑缺血再灌注损伤。
我们证实姜黄素对神经元增殖具有促进作用，对神经元细胞焦亡具有抑制作用。此外，我们发现姜黄素可以改善脑梗死。Western blot 结果显示，姜黄素下调 OGD 和 MCAO 模型中核苷酸结合寡聚结构域样受体蛋白 1（NLRP1）、富含亮氨酸重复序列和吡喃结构域蛋白 1（NLRP1）、半胱天冬酶 1（caspase-1）、Gasdermin D（GSDMD）、白细胞介素-1β（IL-1β）、白细胞介素-6（IL-6）、肿瘤坏死因子-α（TNF-α）和诱导型一氧化氮合酶（iNOS）蛋白的表达。NLRP1 依赖性神经元细胞焦亡在脑缺血再灌注损伤中起重要作用。
姜黄素通过抑制 p38 MAPK 通路有效抑制 NLRP1 依赖性神经元细胞焦亡，从而发挥对脑缺血再灌注损伤的神经保护作用。
