【摘要】 目的：近年来研究表明NOD样受体热蛋白结构域相关蛋白3(NOD-like receptor pyrin domaincontaining protein 3, 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。本研究旨在验证浅蓝菌素(cerulenin)对NLRP3炎症小体介导的疼痛行为的影响及作用机制。方法：本研究采用脂多糖(lipopolysaccharide, 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，并检测背根神经节(dorsal root ganglion, DRG)中NLRP3、含半胱氨酸的天冬氨酸蛋白水解酶1(cysteinyl aspartate specific proteinase-1, Caspase-1)、白细胞介素-1β(interleukin-1β, IL-1β)、消皮素D(gasdermin D, GSDMD)等蛋白表达及细胞因子变化。结果：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转录激活因子3(activating transcription factor 3, ATF3)表达。人单核细胞白血病细胞(tohoku hospital pediatrics-1, THP-1)体外实验亦证实其可阻断NLRP3激活及下游活性氧(reactive oxygen species, ROS)、核因子κB(nuclear factor kappa-B, NF-κB)等信号。结论：浅蓝菌素可通过抑制NLRP3炎症小体激活从而减轻慢性疼痛，为慢性疼痛防治提供新思路。更多还原

【Abstract】 Objective: Recent studies have shown that the NOD-like receptor pyrin domain-containing protein 3(NLRP3) inflammasome contributes to the development of chronic pain by promoting the release of inflammatory factors, and inhibition of its activation may offer novel strategies for pain management. This study verifies the effect and mechanism of cerulenin on NLRP3 inflammasome-mediated pain behavior. Methods: In this study, a mouse model of chronic pain was established using lipopolysaccharide(LPS), and the effects of cerulenin pretreatment and post-treatment on pain behaviors were evaluated. The expressions of NLRP3, cysteinyl aspartate specific proteinase-1(Caspase-1), interleukin-1β(IL-1β), gasdermin D(GSDMD), and related cytokines in the dorsal root ganglion(DRG) were examined. Results: 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 also reduced neuronal excitability and activating transcription factor 3(ATF3) levels. In vitro experiments with tohoku hospital pediatrics-1(THP-1) cells further confirmed that cerulenin could inhibit NLRP3 activation as well as downstream reactive oxygen species(ROS) and nuclear factor kappa-B(NF-κB) signaling. Conclusion: Cerulenin alleviates chronic pain by inhibiting NLRP3 inflammasome activation and related signaling pathways, providing a potential therapeutic strategy for chronic pain management.更多还原