Levo-corydalmine Attenuates Vincristine-Induced Neuropathic Pain in Mice by Upregulating the Nrf2/HO-1/CO Pathway to Inhibit Connexin 43 Expression
Levo-corydalmine Attenuates Vincristine-Induced Neuropathic Pain in Mice by Upregulating the Nrf2/HO-1/CO Pathway to Inhibit Connexin 43 Expression
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左紫堇碱通过上调 Nrf2/HO-1/CO 通路抑制 Connexin 43 表达来减轻长春新碱引起的小鼠神经性疼痛
DOI：
10.1007/s13311-019-00784-7
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发表时间：
2019-10
影响因子：
5.7
通讯作者：
Li Yunman
中科院分区：
文献类型：
--
作者：
Zhou Lin;Ao Luyao;Yan Yunyi;Li Chengyuan;Li Wanting;Ye Anqi;Liu Jihua;Hu Yahui;Fang Weirong;Li Yunman
Antimicrotubulin chemotherapeutic agents, including plant-derived vincaalkaloids such as vincristine, can cause peripheral neuropathic pain. Exogenously activated heme oxygenase 1 (HO-1) is a potential therapy for chemotherapy-induced neuroinflammation. In this study, we investigated a role for Nrf2/HO-1/CO in mediating vincristine-induced neuroinflammation by inhibiting connexin 43 (Cx43) production in the spinal cord following the intrathecal application of the HO-1 inducer protoporphyrin IX cobalt chloride (CoPP) or inhibitor protoporphyrin IX zinc (ZnPP), and we analyzed the underlying mechanisms by which levo-corydalmine (l-CDL, a tetrahydroprotoberberine) attenuates vincristine-induced pain. Treatment with levo-corydalmine or oxycodone hydrochloride (a semisynthetic opioid analgesic, used as a positive control) attenuated vincristine-induced persistent pain hypersensitivity and degeneration of the sciatic nerve. In addition, the increased prevalence of atypical mitochondria induced by vincristine was ameliorated byl-CDL in both A-fibers and C-fibers. Next, we evaluated whether nuclear factor E2-related factor 2 (Nrf2), an upstream activator of HO-1, directly bound to the HO-1 promoter sequence and degraded heme to produce carbon monoxide (CO) following stimulation with vincristine. Notably,l-CDL dose-dependently increased HO-1/CO expression by activating Nrf2 to inhibit Cx43 expression in both the spinal cord and in cultured astrocytes stimulated with TNF-α, corresponding to decreased Cx43-mediated hemichannel. Furthermore,l-CDL had no effect on Cx43 following the silencing of the HO-1 gene. Taken together, our findings reveal a novel mechanism by which Nrf2/HO-1/CO mediates Cx43 expression in vincristine-induced neuropathic pain. In addition, the present findings suggest that l-CDL likely protects against nerve damage and attenuates vincristine-induced neuroinflammation by upregulating Nrf2/HO-1/CO to inhibit Cx43 expression.
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影响因子：
5.3
作者：
Tonkin, Ryan S.;Bowles, Callum;Moalem-Taylor, Gila
通讯作者：
Moalem-Taylor, Gila
影响因子：
20.1
作者：
Piantadosi CA;Carraway MS;Babiker A;Suliman HB
通讯作者：
Suliman HB
影响因子：
4.6
作者：
Boehmerle W;Huehnchen P;Peruzzaro S;Balkaya M;Endres M
通讯作者：
Endres M
影响因子：
3.4
作者：
Castany, Silvia;Carcole, Mireia;Pol, Olga
通讯作者：
Pol, Olga
影响因子：
7.4
作者：
Xue-feng Wu;Wen-tao Liu;Yue-peng Liu;Zhi-jiang Huang;Yan-kai Zhang;Xue-Jun Song
通讯作者：
Xue-feng Wu;Wen-tao Liu;Yue-peng Liu;Zhi-jiang Huang;Yan-kai Zhang;Xue-Jun Song