浅蓝素通过抑制NLRP3炎症小体激活缓解炎症性疼痛的机制研究

Research on the Mechanism of Cerulenin Relieving Inflammatory Pain via Suppressing NLRP3 Inflammasome Activation

摘要:

近年来研究表明 NLRP3炎症小体通过促进炎症因子释放和炎症级联反应,参与慢性疼痛的发生发展,抑制其激活或为新的防治手段。浅蓝菌素(Cerulenin)是一种脂肪酸合成酶抑制剂,具有抗炎作用。本研究采用LPS建立小鼠慢性疼痛模型,分别评估浅蓝菌素预处理及后给药对疼痛行为的影响, 并检测DRG中NLRP3、Caspase-1、IL-1β、GSDMD等蛋白表达及细胞因子变化。结果显示, 浅蓝菌素预处理显著缓解LPS诱导的痛觉敏化,抑制DRG中炎症小体相关分子和部分细胞因子表达, 降低神经元兴奋性及ATF3表达。THP-1细胞体外实验亦证实其可阻断NLRP3激活及下游ROS、NF-κB等信号。结论：浅蓝菌素可通过抑制NLRP3炎症小体激活及相关信号通路, 减轻慢性疼痛, 为慢性疼痛防治提供新思路。

Abstract:

Recent studies have shown that the NLRP3 inflammasome contributes to the development of chronic pain by promoting the release of inflammatory cascades, and inhibition of its activation may offer novel strategies for pain management. Cerulenin, a fatty acid synthase inhibitor, possesses anti-inflammatory properties. In this study, a mouse model of chronic pain was established using LPS, and the effects of cerulenin pretreatment and post-treatment on pain behaviors were evaluated. The expressions of NLRP3, Caspase-1, IL-1β, GSDMD, and related cytokines in the dorsal root ganglion (DRG) was examined. The results showed that cerulenin pretreatment significantly alleviated LPS-induced pain hypersensitivity, suppressed the expression of inflammasome-related proteins and certain cytokines in the DRG, and reduced neuronal excitability and ATF3 levels. In vitro experiments with THP-1 cells further confirmed that cerulenin could inhibit NLRP3 activation as well as downstream ROS and NF-κB signaling. In conclusion, cerulenin alleviates chronic pain by inhibiting NLRP3 inflammasome activation and related signaling pathways, providing a potential therapeutic strategy for chronic pain management.