康乐新通过PKA/NF-κB信号通路调节焦亡和极化，减轻脊髓损伤

IF 4.7 2区医学 Q2 IMMUNOLOGY

International immunopharmacology Pub Date : 2025-03-17 DOI:10.1016/j.intimp.2025.114401

Rongbao Yan , Ye Yuan , Ce Shi , Yang Li , Yang Li , Wenbo Wang , Lei Yang

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引用次数: 0

摘要

背景神经炎症在脊髓损伤（SCI）后复杂的病理生理机制中是必不可少的。越来越多的证据表明，蒽醌类药物对中枢神经系统（CNS）疾病具有抗炎作用。然而，一种新型合成蒽醌类化合物康乐新（Klx）对脊髓损伤的作用尚不清楚。方法采用sc57bl /6小鼠建立挫伤性脊髓损伤模型，探讨Klx在体内的神经保护和炎症调节作用。用BV2细胞体外建立炎症模型。通过评估运动功能和神经病理改变来评估神经保护作用。通过极化和焦亡标记物分析炎症调节，通过转录组测序获得进一步的机制见解。结果sklx促进了脊髓损伤后后肢运动功能的恢复，提高了脊髓损伤后神经元的存活率。体外和体内实验均显示，Klx抑制NLRP3炎性体诱导的焦亡。此外，Klx促进小胶质细胞从促炎M1表型向抗炎M2表型极化。机制上，Klx增强PKA磷酸化，抑制NF-κB和i -κB α磷酸化，从而减少NF-κB核易位。结论klx对脊髓损伤具有神经保护和炎症调节作用，可能是一种有前景的治疗方案。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

Kanglexin attenuates spinal cord injury by modulating pyroptosis and polarization via the PKA/NF-κB signaling pathway

查看原文本刊更多论文

Kanglexin attenuates spinal cord injury by modulating pyroptosis and polarization via the PKA/NF-κB signaling pathway

Background

Neuroinflammation is essential for intricate pathophysiologic mechanisms after spinal cord injury (SCI). Increasing evidence suggests that anthraquinones possess anti-inflammatory properties in central nervous system (CNS) disorders. However, the effects of Kanglexin (Klx), a novel synthetic anthraquinone compound, on SCI remain unknown.

Methods

C57BL/6 mice were utilized to establish a contused SCI model to explore the in vivo neuroprotective and inflammatory modulatory effects of Klx. An inflammation model was also created in vitro using BV2 cells. Neuroprotective effects were assessed by evaluating motor function and neuropathologic alterations. Inflammation modulation was analyzed through markers of polarization and pyroptosis, with further mechanistic insights obtained via transcriptome sequencing.

Results

Klx facilitated the recovery of hindlimb locomotor function and improved neuronal survival after SCI. Both in vitro and in vivo assays revealed that Klx inhibited NLRP3 inflammasome-induced pyroptosis. In addition, Klx promoted the polarization of microglia from the proinflammatory M1 phenotype to the anti-inflammatory M2 phenotype. Mechanistically, Klx enhanced PKA phosphorylation and suppressed NF-κB and IκBα phosphorylation, thereby reducing NF-κB nuclear translocation.

Conclusion

Klx demonstrated neuroprotective and inflammation-modulating effects on SCI, suggesting that it might offer a promising therapeutic alternative for SCI.

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来源期刊

International immunopharmacology 医学-免疫学

CiteScore

8.40

自引率

3.60%

发文量

935

审稿时长

53 days

期刊介绍： International Immunopharmacology is the primary vehicle for the publication of original research papers pertinent to the overlapping areas of immunology, pharmacology, cytokine biology, immunotherapy, immunopathology and immunotoxicology. Review articles that encompass these subjects are also welcome. The subject material appropriate for submission includes: • Clinical studies employing immunotherapy of any type including the use of: bacterial and chemical agents; thymic hormones, interferon, lymphokines, etc., in transplantation and diseases such as cancer, immunodeficiency, chronic infection and allergic, inflammatory or autoimmune disorders. • Studies on the mechanisms of action of these agents for specific parameters of immune competence as well as the overall clinical state. • Pre-clinical animal studies and in vitro studies on mechanisms of action with immunopotentiators, immunomodulators, immunoadjuvants and other pharmacological agents active on cells participating in immune or allergic responses. • Pharmacological compounds, microbial products and toxicological agents that affect the lymphoid system, and their mechanisms of action. • Agents that activate genes or modify transcription and translation within the immune response. • Substances activated, generated, or released through immunologic or related pathways that are pharmacologically active. • Production, function and regulation of cytokines and their receptors. • Classical pharmacological studies on the effects of chemokines and bioactive factors released during immunological reactions.