Inhibition of the spinal astrocytic JNK/MCP-1 pathway activation correlates with the analgesic effects of tanshinone IIA sulfonate in neuropathic pain.
Inhibition of the spinal astrocytic JNK/MCP-1 pathway activation correlates with the analgesic effects of tanshinone IIA sulfonate in neuropathic pain.
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脊髓星形细胞 JNK/MCP-1 通路激活的抑制与丹参酮 IIA 磺酸盐在神经性疼痛中的镇痛作用相关
DOI：
10.1186/s12974-015-0279-7
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发表时间：
2015-03-25
影响因子：
9.3
通讯作者：
Li WY
中科院分区：
文献类型：
--
作者：
Tang J;Zhu C;Li ZH;Liu XY;Sun SK;Zhang T;Luo ZJ;Zhang H;Li WY
背景由于缺乏有效的药物，神经性疼痛（NP）的治疗仍然具有挑战性。越来越多的证据表明，神经胶质细胞介导的炎症反应在 NP 的发生和发展中发挥着关键作用。此外，据报道，星形胶质细胞中 c-Jun N 末端激酶 (JNK)/单核细胞趋化蛋白-1 (MCP-1) 通路的激活对于脊髓神经结扎 (SNL) 后脊髓星形胶质细胞的激活和神经病理性疼痛的发展至关重要。丹参酮 IIA 是中药丹参的主要活性成分，具有有效的免疫抑制活性。本研究旨在评估腹腔注射丹参酮IIA磺酸盐(TIIAS)是否对SNL诱发的神经病理性疼痛具有镇痛作用，以及抑制星形细胞活化和JNK/MCP-1通路是否参与TIIAS的镇痛作用。方法通过行为测试评估TIIAS对SNL诱发的机械性异常性疼痛的影响。采用免疫荧光组织化学染色检测脊髓星形胶质细胞和脊髓pJNK表达及定位的变化。免疫荧光组织化学和蛋白质印迹分析用于量化 TIIAS 给药后 SNL 诱导的脊髓 pJNK 表达。采用酶联免疫吸附试验（ELISA）检测SNL诱导的脊髓中促炎细胞因子和MCP-1的表达。结果我们的结果表明，腹腔内TIIAS上调了NP的机械缩爪阈值（PWT），而星形胶质细胞的活化受到抑制，并伴随着IL-1β和TNF-α表达的下调，以及脊髓背角JNK的磷酸化。此外，MCP-1 的释放呈剂量依赖性减少。 TIIAS和JNK抑制剂(SP600125)联合治疗后，与TIIAS治疗组相比，机械PWT和MCP-1表达没有观察到显着增加。结论目前的结果表明，TIIAS对神经性疼痛的镇痛作用主要是通过下调SNL诱导的星形胶质细胞活化来介导的，而这通过抑制JNK/MCP-1途径来介导。
BackgroundNeuropathic pain (NP) continues to be challenging to treat due to lack of effective drugs. Accumulating evidence elucidated that glia-mediated inflammatory reactions play a pivotal role in the introduction and development of NP. Besides, activation of the c-Jun N-terminal kinase (JNK)/monocyte chemoattractant protein-1 (MCP-1) pathway in astrocytes has been reported to be critical for spinal astrocytic activation and neuropathic pain development after spinal nerve ligation (SNL). Tanshinone IIA, a major active component of a traditional Chinese drug, Danshen, possesses potent immuno-suppressive activities. The present study was undertaken to assess whether intraperitoneal administration of tanshinone IIA sulfonate (TIIAS) has analgesic effect on SNL-induced neuropathic pain and whether the inhibition of astrocytic activation and JNK/MCP-1 pathway is involved in the analgesic effect of TIIAS.MethodsThe effects of TIIAS on SNL-induced mechanical allodynia were assessed by behavioral testing. Immunofluorescence histochemical staining was used to detect changes of spinal astrocytes and spinal pJNK expression and localization. Immunofluorescence histochemistry and Western blot analysis were used to quantify the SNL-induced spinal pJNK expression after TIIAS administration. Enzyme-linked immunosorbent assay (ELISA) was used to detect the SNL-induced spinal expression of pro-inflammatory cytokines and MCP-1.ResultsOur results indicated that intraperitoneal TIIAS up-regulated the mechanical paw withdrawal threshold (PWT) of NP, while astrocytic activation was suppressed and accompanied by the down-regulation of IL-1β and TNF-α expression, as well as JNK phosphorylation in the spinal dorsal horn. Additionally, the release of MCP-1 was dose dependently decreased. After co-treatment with TIIAS and JNK inhibitor (SP600125), no significant increases in mechanical PWT and MCP-1 expression were observed compared with the TIIAS-treated group.ConclusionsThe present results suggest that the analgesic effects of TIIAS in neuropathic pain are mainly mediated by the down-regulation of SNL-induced astrocytic activation, which is via the inhibition of JNK/MCP-1 pathway.
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影响因子：
4.2
作者：
HAMM, RJ;PIKE, BR;JENKINS, LW
通讯作者：
JENKINS, LW
影响因子：
7.2
作者：
Ahn, Young-Min;Kim, Su Kang;Lee, Byung-Cheol
通讯作者：
Lee, Byung-Cheol
影响因子：
6
作者：
Jha MK;Jeon S;Suk K
通讯作者：
Suk K
影响因子：
5.9
作者：
O'Connor, Alec B.;Dworkin, Robert H.
通讯作者：
Dworkin, Robert H.
影响因子：
7.4
作者：
Ma, WY;Quirion, R
通讯作者：
Quirion, R