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姜黄素可抑制牙髓炎后肥大细胞介导的神经免疫反应。

Curcumin inhibits the neuroimmune response mediated by mast cells after pulpitis.

作者信息

Dong Ming, Tang Jing, Li Lu-Jia, Dai Ting, Zuo Yi-Yan, Jin Hai-Wei

机构信息

Dalian Medical University, School of Stomatology, Dalian, China.

Suqian Stomatological Hospital, Suqian, China.

出版信息

J Appl Oral Sci. 2024 Sep 9;32:e20230456. doi: 10.1590/1678-7757-2023-0456. eCollection 2024.

Abstract

OBJECTIVE

To analyze the effect of mast cells (MCs) in neurogenic inflammation and the neuroimmune response of trigeminal ganglia (TG) due to pulpitis and detect the regulatory effect of curcumin (Cur) on neuroimmune responses induced by pulpitis.

METHODOLOGY

Immunohistochemistry, toluidine blue staining (TB), and other methods were used to detect the dynamic changes of MCs, as well as tryptase expression changes and protease activated receptor 2 (PAR2) and calcitonin gene-related peptide (CGRP) levels in the neuroimmune response induced by pulpitis. After administering Cur by intraperitoneal injection, the expression levels of Toll-like receptor 4 (TLR4), CGRP, glial fibrillary acidic protein (GFAP), fractalkine (CX3CL1), Tumor necrosis factor (TNF-α), and other factors were examined in the TG of pulpitis-induced rats.

RESULTS

After pulpitis induction, the expression of CGRP-positive neurons and GFAP-positive soluble guanylate cyclase (SGC) in the TG significantly increased. A large number of MCs underwent degranulation. MCs were scattered between the CGRP-positive nerve fibers. MCs showing a typical degranulated state within the TG significantly increased and tryptase-positive MCs surrounded the TG nerve fibers and neurons. After treatment with Cur, the inflammatory response in the periodontal bone induced by pulpitis decreased and promoted early tissue repair. The expression of TNF-α significantly decreased as did degranulation of MCs. In contrast, the expression of CGRP, TLR4-positive neurons, activated SGCs, and PAR2-positive TG neurons significantly decreased. MCs could participate in the neuroimmune response induced by pulpitis by the tryptase signaling pathway.

CONCLUSION

Importantly, Cur inhibited the degranulation of MCs, downregulated the expression of tryptase and PAR2 in the TG, and attenuated the activation response of osteoclasts in the apical periodontium.

摘要

目的

分析肥大细胞(MCs)在神经源性炎症及牙髓炎所致三叉神经节(TG)神经免疫反应中的作用,并检测姜黄素(Cur)对牙髓炎诱导的神经免疫反应的调节作用。

方法

采用免疫组织化学、甲苯胺蓝染色(TB)等方法检测MCs的动态变化,以及牙髓炎诱导的神经免疫反应中类胰蛋白酶表达变化、蛋白酶激活受体2(PAR2)和降钙素基因相关肽(CGRP)水平。腹腔注射Cur后,检测牙髓炎诱导大鼠TG中Toll样受体4(TLR4)、CGRP、胶质纤维酸性蛋白(GFAP), 趋化因子(CX3CL1)、肿瘤坏死因子(TNF-α)等因子的表达水平。

结果

诱导牙髓炎后,TG中CGRP阳性神经元和GFAP阳性可溶性鸟苷酸环化酶(SGC)的表达显著增加。大量MCs发生脱颗粒。MCs散在于CGRP阳性神经纤维之间。TG内呈现典型脱颗粒状态的MCs显著增多,类胰蛋白酶阳性的MCs围绕TG神经纤维和神经元。Cur治疗后,牙髓炎诱导的牙周骨炎症反应减轻,促进了早期组织修复。TNF-α的表达显著降低,MCs的脱颗粒也减少。相反,CGRP、TLR4阳性神经元、活化的SGC和PAR2阳性TG神经元的表达显著降低。MCs可通过类胰蛋白酶信号通路参与牙髓炎诱导的神经免疫反应。

结论

重要的是,Cur抑制了MCs的脱颗粒,下调了TG中类胰蛋白酶和PAR2的表达,并减弱了根尖牙周膜中破骨细胞的激活反应。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d27/11464083/e7af6aae2848/1678-7757-jaos-32-e20240456-gf01.jpg

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