关键词: Caspase-1 Drug-resistant epilepsy NOD-like receptor family, pyrin domain-containing 3 inflammasome Silent information regulator 1

Mesh : Humans Inflammasomes / metabolism NLR Family, Pyrin Domain-Containing 3 Protein / metabolism NLR Proteins Pyrin Domain Sirtuin 1 / metabolism Hippocampal Sclerosis Caspase 1 / metabolism Interleukin-1beta / metabolism

来  源:   DOI:10.1016/j.eplepsyres.2024.107338

Abstract:
BACKGROUND: The NOD-like receptor family, pyrin domain-containing 3 (NLRP3) inflammatory pathway is implicated in the development of epilepsy and can be suppressed by the activation of the silent information regulator 1 (SIRT1). However, the expression and correlation of the NLRP3 pathway and SIRT1 in drug-resistant epilepsy (DRE) remain unknown.
METHODS: This study evaluated the histopathology of the cerebral cortex from nine patients with DRE and eight patients with cavernous haemangioma undergoing surgical treatment. It analysed the expression of the NLRP3, interleukin-1β (IL-1β), caspase-1 and SIRT1 using immunohistochemistry. Additionally, the contents of NLRP3, caspase-1, IL-1β and SIRT1 in the serum samples of the included study participants were determined using ELISA method. The correlation between the NLRP3 pathway and the SIRT1 was assessed using Spearman\'s correlation analysis.
RESULTS: The expression of NLRP3, caspase-1 and IL-1β in the cerebral cortex of patients with DRE was elevated, with the NLRP3 expression being negatively correlated with the SIRT1 expression. Furthermore, IL-1β in serum was upregulated in patients with DRE. The correlation between the content of serum SIRT1 and NLRP3, caspase-1 and IL-1β in patients with DRE was not significant. Notably, serum caspase-1 levels were obviously higher in patients with bilateral hippocampal sclerosis than in patients with unilateral hippocampal sclerosis.
CONCLUSIONS: The current results indicate that the expression of the NLRP3/caspase-1/IL-1β pathway is significantly upregulated in patients with DRE and that it is partially correlated with the SIRT1 expression. This study is important for understanding the pathophysiology of DRE and developing new treatment strategies for it.
摘要:
背景:NOD样受体家族,含pyrin结构域3(NLRP3)的炎症途径与癫痫的发展有关,并且可以通过沉默信息调节因子1(SIRT1)的激活来抑制。然而,NLRP3通路和SIRT1在耐药癫痫(DRE)中的表达和相关性尚不清楚.
方法:本研究评估了9例DRE患者和8例接受手术治疗的海绵状血管瘤患者大脑皮质的组织病理学。它分析了NLRP3,白细胞介素-1β(IL-1β)的表达,caspase-1和SIRT1使用免疫组织化学。此外,采用ELISA法测定纳入研究对象血清中NLRP3、caspase-1、IL-1β和SIRT1的含量。NLRP3通路与SIRT1的相关性采用Spearman相关分析。
结果:DRE患者大脑皮质NLRP3、caspase-1和IL-1β的表达升高,NLRP3表达与SIRT1表达呈负相关。此外,DRE患者血清IL-1β水平上调。DRE患者血清SIRT1、NLRP3、caspase-1、IL-1β含量的相关性均无统计学意义。值得注意的是,双侧海马硬化患者血清caspase-1水平明显高于单侧海马硬化患者。
结论:目前的结果表明,在DRE患者中,NLRP3/caspase-1/IL-1β途径的表达显着上调,并且与SIRT1表达部分相关。这项研究对于了解DRE的病理生理学和开发新的治疗策略非常重要。
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