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聚肌胞苷酸通过TLR3/TRIF信号通路抑制神经炎症来减轻硝酸甘油诱导的偏头痛。

Poly-IC Alleviates Nitroglycerin-Induced Migraine by Inhibiting Neuroinflammation via TLR3/TRIF Signaling Pathway.

作者信息

Hong Ye, Ma Mengmeng, Li Changling, Zhang Yang, Li Yanbo, Chen Ning, Fang Jinghuan, He Li

机构信息

Department of Neurology, West China Hospital of Sichuan University, Chengdu, China.

Department of Neurology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.

出版信息

CNS Neurosci Ther. 2025 May;31(5):e70444. doi: 10.1111/cns.70444.

DOI:10.1111/cns.70444
PMID:40406905
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12099309/
Abstract

AIMS

Toll-like receptors (TLRs) play critical roles in pain modulation and immune responses. Polyinosinic-polycytidylic acid (Poly-IC), a TLR3-specific ligand, has shown promise in exerting neuroprotective effects, as it mitigates inflammation in several diseases. Considering that sterile neurogenic inflammation is involved in the pathogenesis of migraine, we explored the impact of Poly-IC on episodic migraine treatment and the potential mechanisms involved.

METHODS

Episodic migraine was induced in male rats via a single intraperitoneal injection of nitroglycerin. Poly-IC (with or without a TLR3 inhibitor) treatment was performed before migraine induction. Pain was assessed according to the mechanical sensitivity threshold, head-directed grooming, and the Rat Grimace Scale. The expression of TLR3 and its downstream molecule TRIF was subsequently examined, after which calcitonin gene-related peptide (CGRP), c-fos, and proinflammatory cytokine expression was assessed. Moreover, TRIF expression in primary cultured neurons was knocked down by shRNA in vitro to further explore the mechanisms by which Poly-IC mediates migraine-like inflammation.

RESULTS

Poly-IC treatment significantly upregulated TLR3/TRIF expression, reduced the production of CGRP, c-fos, and inflammatory cytokines, and alleviated allodynia in an animal model of migraine. Moreover, TRIF knockdown blunted the anti-inflammatory effects of Poly-IC treatment in primary cultured neurons.

CONCLUSIONS

Poly-IC exerts therapeutic effects against neurogenic inflammation via the TLR3/TRIF signaling pathway in an episodic migraine model.

摘要

目的

Toll样受体（TLRs）在疼痛调节和免疫反应中起关键作用。聚肌苷酸-聚胞苷酸（Poly-IC）是一种TLR3特异性配体，已显示出具有神经保护作用的前景，因为它可减轻多种疾病中的炎症。鉴于无菌性神经源性炎症参与偏头痛的发病机制，我们探讨了Poly-IC对发作性偏头痛治疗的影响及其潜在机制。

方法

通过单次腹腔注射硝酸甘油在雄性大鼠中诱发发作性偏头痛。在偏头痛诱导前进行Poly-IC（有或无TLR3抑制剂）治疗。根据机械敏感性阈值、头部梳理行为和大鼠面部表情量表评估疼痛。随后检测TLR3及其下游分子TRIF的表达，之后评估降钙素基因相关肽（CGRP）、c-fos和促炎细胞因子的表达。此外，在体外通过短发夹RNA敲低原代培养神经元中的TRIF表达，以进一步探索Poly-IC介导偏头痛样炎症的机制。

结果

在偏头痛动物模型中，Poly-IC治疗显著上调TLR3/TRIF表达，减少CGRP、c-fos和炎性细胞因子的产生，并减轻异常性疼痛。此外，TRIF敲低减弱了Poly-IC治疗在原代培养神经元中的抗炎作用。

结论

在发作性偏头痛模型中，Poly-IC通过TLR3/TRIF信号通路对神经源性炎症发挥治疗作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c426/12099309/6259c08be7cf/CNS-31-e70444-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c426/12099309/cf39b017fbbb/CNS-31-e70444-g001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c426/12099309/766e4b2db2ec/CNS-31-e70444-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c426/12099309/aed66c7fca8e/CNS-31-e70444-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c426/12099309/6259c08be7cf/CNS-31-e70444-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c426/12099309/cf39b017fbbb/CNS-31-e70444-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c426/12099309/4b7392658932/CNS-31-e70444-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c426/12099309/03923edb3134/CNS-31-e70444-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c426/12099309/266a6105c0f3/CNS-31-e70444-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c426/12099309/766e4b2db2ec/CNS-31-e70444-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c426/12099309/aed66c7fca8e/CNS-31-e70444-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c426/12099309/6259c08be7cf/CNS-31-e70444-g007.jpg

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