Inhibition of apoptosis signal-regulating kinase by paeoniflorin attenuates neuroinflammation and ameliorates neuropathic pain
Inhibition of apoptosis signal-regulating kinase by paeoniflorin attenuates neuroinflammation and ameliorates neuropathic pain
复制标题
芍药苷抑制凋亡信号调节激酶可减轻神经炎症并改善神经性疼痛
DOI：
10.1186/s12974-019-1476-6
复制
发表时间：
2019-04-11
影响因子：
9.3
通讯作者：
Zhang, Guang-Qin
中科院分区：
文献类型：
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作者：
Zhou, Danli;Zhang, Siqi;Zhang, Guang-Qin
背景神经病理性疼痛是一个严重的临床问题，亟待解决。ASK 1是p38和JNK的上游蛋白，在慢性疼痛的诱导和维持过程中的神经炎症中起重要作用。因此，抑制ASK 1可能是神经病理性疼痛的一种新的治疗方法。在这里，我们的目的是调查芍药苷对ASK 1和神经病理性pain.MethodsThe大鼠的机械和热阈值的影响进行了测量，使用Von Frey测试。细胞信号进行了分析，使用Western印迹和免疫组化。ResultsChronic constrictive injury（CCI）手术成功地降低了大鼠的机械和热阈值，并降低了大鼠脊髓中ASK 1的磷酸化。ASK 1抑制剂NQDI 1可减轻神经病理性疼痛并降低p-p38和p-JNK的表达。芍药苷模拟ASK 1抑制剂NQDI 1并抑制ASK 1磷酸化。芍药苷可降低p-p38和p-JNK的表达，延缓神经病理性疼痛的进展，减轻神经病理性疼痛。结论芍药苷通过抑制大鼠神经病理性疼痛模型中ASK 1的磷酸化，对神经病理性疼痛有一定的治疗作用。
BackgroundNeuropathic pain is a serious clinical problem that needs to be solved urgently. ASK1 is an upstream protein of p38 and JNK which plays important roles in neuroinflammation during the induction and maintenance of chronic pain. Therefore, inhibition of ASK1 may be a novel therapeutic approach for neuropathic pain. Here, we aim to investigate the effects of paeoniflorin on ASK1 and neuropathic pain.MethodsThe mechanical and thermal thresholds of rats were measured using the Von Frey test. Cell signaling was assayed using western blotting and immunohistochemistry.ResultsChronic constrictive injury (CCI) surgery successfully decreased the mechanical and thermal thresholds of rats and decreased the phosphorylation of ASK1 in the rat spinal cord. ASK1 inhibitor NQDI1 attenuated neuropathic pain and decreased the expression of p-p38 and p-JNK. Paeoniflorin mimicked ASK1 inhibitor NQDI1 and inhibited ASK1 phosphorylation. Paeoniflorin decreased the expression of p-p38 and p-JNK, delayed the progress of neuropathic pain, and attenuated neuropathic pain. Paeoniflorin reduced the response of astrocytes and microglia to injury, decreased the expression of IL-1β and TNF-α, and downregulated the expression of CGRP induced by CCI.ConclusionsPaeoniflorin is an effective drug for the treatment of neuropathic pain in rats via inhibiting the phosphorylation of ASK1, suggesting it may be effective in patients with neuropathic pain.