Fexofenadine Protects Against Intervertebral Disc Degeneration Through TNF Signaling.
Fexofenadine Protects Against Intervertebral Disc Degeneration Through TNF Signaling.
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非索非那定通过 TNF 信号传导防止椎间盘退变。
DOI：
10.3389/fcell.2021.687024
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发表时间：
2021
影响因子：
5.5
通讯作者：
Cheng L
中科院分区：
文献类型：
--
作者：
Liu K;Wei J;Li G;Liu R;Zhao D;Zhang Y;Shi J;Xie Q;Cheng L
目的：非索非那定（FFD）是一种具有抗炎作用的抗组胺药。椎间盘退变过程涉及炎症反应，肿瘤坏死因子-α（tumor necrosis factor-α，TNF-α）在其中起重要作用。本研究旨在探讨FFD在IVD变性病理过程中的作用。方法：采用番红O染色法对椎间盘软骨组织进行测量。苏木精-伊红（H&E）染色用于确定椎间盘结构。利用大鼠针刺模型研究FFD在体内椎间盘退变中的作用。采用免疫印迹法、免疫组化法和免疫荧光染色法检测炎性分子的表达。ELISA法检测细胞因子的释放。分析实时PCR测定以确定分子的转录表达。结果：TNF-α升高可导致椎间盘炎性退变，而FFD对TNF-α诱导的椎间盘退变有保护作用。机制研究发现FFD至少通过两条途径发挥椎间盘保护作用。(a)FFD抑制TNF-α介导的细胞外基质（ECM）降解，（B）FFD挽救了TNF-α诱导的椎间盘退变炎症。FFD通过cPLA 2/NF-κB信号通路抑制TNF-α介导的椎间盘退变。结论：FFD通过一种新的机制提供了治疗椎间盘退变的另一种选择。此外，FFD也可能是治疗其他炎症相关疾病（包括IVD变性）的潜在靶点。
Objective: Fexofenadine (FFD) is an antihistamine drug with an anti-inflammatory effect. The intervertebral disc (IVD) degeneration process is involved in inflammation in which tumor necrosis factor-α (TNF-α) plays an important role. This study aims to investigate the role of FFD in the pathological process of IVD degeneration. Methods: Safranin O staining was used for the measurement of cartilageous tissue in the disc. Hematoxylin-Eosin (H&E) staining was used to determine the disc construction. A rat needle puncture model was taken advantage of to examine the role of FFD in disc degeneration in vivo. Western Blotting assay, immunochemistry, and immunoflurence staining were used for the determination of inflammatory molecules. ELISA assay was performed to detect the release of inflammatory cytokines. A real-time PCR assay was analyzed to determine the transcriptional expressions of molecules. Results: Elevated TNF-α resulted in inflammatory disc degeneration, while FFD protected against TNF-α-induced IVD degeneration. Mechanism study found FFD exhibited a disc protective effect through at least two pathways. (a) FFD inhibited TNF-α-mediated extracellular matrix (ECM) degradation and (b) FFD rescued TNF-α induced inflammation in disc degeneration. Furthermore, the present study found that FFD suppressed TNF-α mediated disc degeneration via the cPLA2/NF-κB signaling pathway. Conclusions: FFD provided another alternative for treating disc degeneration through a novel mechanism. Additionally, FFD may also be a potential target for the treatment of other inflammatory-related diseases, including IVD degeneration.
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