Jia Yujie, Xue Kun, Luo Ying, Liu Chang
Department of Neurology, the First Affiliated Hospital of Jinzhou Medical University, No. 2, Section 5, Renmin Street, Guta District, Jinzhou City, 121001, Liaoning Province, China.
Exp Brain Res. 2023 Mar;241(3):839-849. doi: 10.1007/s00221-023-06566-0. Epub 2023 Feb 7.
A recent study confirmed that thiolutin is effective in the treatment of nucleotide-binding domain-like receptor protein 3 (NLRP3)-related inflammatory diseases. Nevertheless, whether thiolutin (THL) is involved in the regulation of NLRP3 inflammasome in ischemic stroke is not known. The murine neuronal cell oxygen-glucose deprivation (OGD) model was first established, and then different concentrations (25 nM and 50 nM) of THL were administered for 48 h incubation, respectively. Subsequently, cell viability and toxicity, and the levels of intracellular inflammatory factors interleukin-1β (IL-1β), interleukin-18 (IL-18), oxidative stress factors superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT) and malondialdehyde (MDA), and NLRP3 inflammasome activation-related proteins pro-caspase, caspase-1, apoptosis-associated speck like-protein (ASC) and NLRP3 were examined, respectively. We further established the mouse middle cerebral artery occlusion (MCAO) model to evaluate the therapeutic effects of THL on cerebral infarction like behaviors in mice and the preventive effects on NLRP3 inflammasome activation in vivo. Cell cytotoxic, and the levels of inflammatory factors and oxidative stress were conspicuously increased, and NLRP3 inflammasome was materially activated in the OGD-induced cell model and MCAO-established mouse model, which were partially countered by THL treatment. Besides, intraperitoneal injection of THL could prominently reduce the cerebral infarct volume and neuromotor deficit scores in MCAO mice. The present study confirmed that THL attenuated neuronal and cerebral inflammatory injury caused by OGD and MCAO models in mice through restraining NLRP3 inflammasome activation in vitro and in vivo.
最近的一项研究证实，硫藤黄菌素对治疗核苷酸结合寡聚化结构域样受体蛋白3（NLRP3）相关的炎症性疾病有效。然而，硫藤黄菌素（THL）是否参与缺血性中风中NLRP3炎性小体的调节尚不清楚。首先建立小鼠神经元细胞氧糖剥夺（OGD）模型，然后分别给予不同浓度（25 nM和50 nM）的THL孵育48小时。随后，分别检测细胞活力和毒性、细胞内炎性因子白细胞介素-1β（IL-1β）、白细胞介素-18（IL-18）、氧化应激因子超氧化物歧化酶（SOD）、谷胱甘肽过氧化物酶（GSH-Px）、过氧化氢酶（CAT）和丙二醛（MDA）的水平，以及NLRP3炎性小体激活相关蛋白前半胱天冬酶、半胱天冬酶-1、凋亡相关斑点样蛋白（ASC）和NLRP3的水平。我们进一步建立了小鼠大脑中动脉闭塞（MCAO）模型，以评估THL对小鼠脑梗死样行为的治疗作用以及对体内NLRP3炎性小体激活的预防作用。在OGD诱导的细胞模型和MCAO建立的小鼠模型中，细胞毒性以及炎性因子和氧化应激水平显著升高，NLRP3炎性小体被实质性激活，而THL处理可部分对抗这些变化。此外，腹腔注射THL可显著降低MCAO小鼠的脑梗死体积和神经运动功能缺损评分。本研究证实，THL通过在体外和体内抑制NLRP3炎性小体激活，减轻了OGD和MCAO模型对小鼠造成的神经元和脑部炎性损伤。
