Tanshinone IIA represses inflammatory response and reduces radiculopathic pain by inhibiting IRAK-1 and NF-κB/p38/JNK signaling
Tanshinone IIA represses inflammatory response and reduces radiculopathic pain by inhibiting IRAK-1 and NF-κB/p38/JNK signaling
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DOI：
10.1016/j.intimp.2015.06.032
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发表时间：
2015-09-01
影响因子：
5.6
通讯作者：
Zhang, Mengyuan
中科院分区：
文献类型：
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作者：
Li, Wei;Zhang, Yu;Zhang, Mengyuan
椎间盘（IVD）疾病是椎间盘衰竭和腰痛的最常见原因，其特征在于成人椎间盘的年龄相关变化。本研究旨在通过体外培养的IVD细胞和体内动物模型研究丹参酮IIA（TSA）的抗炎和抗分解代谢活性，探讨其治疗IVD疾病的潜力。在IVD细胞中通过IL-1 β诱导炎症反应后，在存在或不存在TSA的情况下研究了炎症介质的活性和表达以及可能涉及的途径。p38-MAPK抑制剂SB 239063也被用于研究MAPK信号通路在所观察到的效应中的参与。同时采用Sprague道利大鼠的vonFrey细丝实验分析TSA的镇痛作用。我们的研究结果表明，TSA显着抑制促炎介质和基质金属蛋白酶在体外的表达，以及在体内的神经根性疼痛，可能是通过调节白细胞介素-1受体相关激酶1（IRAK-1）及其下游效应子p38，JNK和NF-κ B B的活性。我们目前的研究有力地证明了TSA在治疗退行性椎间盘疾病的炎症和疼痛方面的潜力。(C)2015 Elsevier B. V.版权所有。
Intervertebral disc (IVD) disease, a most common cause of disc failure and low back pain, is characterized by age-related changes in the adult disc. In this study we aimed to investigate the potential of Tanshinone IIA (TSA) for the treatment of IVD disease, through exploring its anti-inflammatory and anti-catabolic activities in both in vitro IVD cell culture and in vivo animal models. After the inflammatory response was induced in IVD cells by IL-1 beta, the activity and expression of inflammatory mediators, and potentially involved pathways were investigated in the presence or absence of TSA. The p38-MAPK inhibitor, SB239063, was also used to investigate the involvement of the MAPK signaling pathway in the observed effects. Meanwhile, the analgesic properties of TSA were analyzed by the von Frey filament test in Sprague Dawley rats. Our results indicated that TSA significantly inhibited the expression of pro-inflammatory mediators and matrix metalloproteinases in vitro, as well as radiculopathic pain in vivo, probably by modulation of the activity of interleukin-1 receptor-associated kinase 1 (IRAK-1) and its downstream effectors p38, JNK and NF-kappa B. Our current study strongly demonstrates the potential of TSA for the treatment of inflammation and followed pain in degenerative disc disease. (C) 2015 Elsevier B.V. All rights reserved.