一种特异性NLRP3抑制剂减轻戊四氮诱导的癫痫严重程度的分子机制
Molecular Mechanism of a Specific NLRP3 Inhibitor to Alleviate Seizure Severity Induced by Pentylenetetrazole.
作者信息
Shen Kai, Jiang Wanzhi, Zhang Chunyan, Cai Liangliang, Wang Qin, Yu Haiyan, Tang Zhiyuan, Gu Zhifeng, Chen Bohua
机构信息
Department of Pharmacy, Affiliated Hospital of Nantong University, Nantong, China.
Department of Pharmacy, Nantong Health College of Jiangsu Province, Nantong, China.
出版信息
Curr Mol Pharmacol. 2021 Oct 25;14(4):579-586. doi: 10.2174/1874467213666200810140749.
BACKGROUND
While our previous research has demonstrated that the NLRP3 inflammasome is involved in epilepsy progression, the effects of the specific NLRP3 inhibitor CY-09 remain poorly understood. Therefore, the aim of the present study was to investigate the efficacy of CY-09 against pentylenetetrazole (PTZ)-induced neuronal loss in mice.
METHODS
The expressions of the proinflammatory factors interleukin-1β and interleukin-18 were examined by western blot and enzyme-linked immunosorbent assays. Western blot analysis was applied to detect the level of astrocyte activation. Neuronal apoptosis was determined by western blot analysis combined with immunostaining specific for neuronal nuclei.
RESULTS
We found that CY-09 ameliorated the progression of the kindling process and inhibited PTZ-induced neuronal loss by attenuating the activation of astrocytes and the secretion of NLRP3- dependent neuroinflammation. Conclumsion: These findings indicate that CY-09 may represent an important treatment agent for epilepsy and other NLRP3 inflammasome-associated diseases.
背景
虽然我们之前的研究表明NLRP3炎性小体参与癫痫进展，但特异性NLRP3抑制剂CY-09的作用仍知之甚少。因此，本研究的目的是探讨CY-09对戊四氮（PTZ）诱导的小鼠神经元损失的疗效。
方法
通过蛋白质免疫印迹法和酶联免疫吸附测定法检测促炎因子白细胞介素-1β和白细胞介素-18的表达。应用蛋白质免疫印迹分析检测星形胶质细胞活化水平。通过蛋白质免疫印迹分析结合针对神经元细胞核的免疫染色来确定神经元凋亡。
结果
我们发现CY-09改善了点燃过程的进展，并通过减弱星形胶质细胞的活化和NLRP3依赖性神经炎症的分泌来抑制PTZ诱导的神经元损失。结论：这些发现表明CY-09可能是癫痫和其他NLRP3炎性小体相关疾病的重要治疗药物。 （注：原文中“Conclumsion”拼写错误，应为“Conclusion”）
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