Dehydrocorydaline attenuates bone cancer pain by shifting microglial M1/M2 polarization toward the M2 phenotype.
Dehydrocorydaline attenuates bone cancer pain by shifting microglial M1/M2 polarization toward the M2 phenotype.
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脱氢紫堇碱通过将小胶质细胞 M1/M2 极化转向 M2 表型来减轻骨癌疼痛
DOI：
10.1177/1744806918781733
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发表时间：
2018-01
期刊：
影响因子：
3.3
通讯作者：
Gu X
中科院分区：
文献类型：
--
作者：
Huo W;Zhang Y;Liu Y;Lei Y;Sun R;Zhang W;Huang Y;Mao Y;Wang C;Ma Z;Gu X
由于缺乏对机制的了解，骨癌疼痛仍然是原发性或转移性骨癌患者的主要挑战。先前的研究揭示了在神经损伤引起的神经病理性疼痛中脊髓中小胶质细胞的两种不同的功能极化状态（经典激活的M1和交替激活的M2）。然而，脊髓中的小胶质细胞是否具有M1和M2表型并有助于骨癌疼痛的发展仍不清楚。在这项研究中，我们使用了一个小鼠模型与骨癌疼痛的发展过程中，在脊髓中的小胶质细胞的M1/M2极化的特点，并探讨脱氢皮质醇，从地黄中分离出的生物碱成分对骨癌疼痛的抗伤害性感受作用。结果表明，在骨癌痛发生发展过程中，脊髓小胶质细胞M1极化增强，M2极化减弱，同时IL-1β过度表达，IL-10表达受到抑制。10 mg/kg去氢肾上腺素腹腔注射在骨肉瘤细胞移植后第14 d具有明显的抗伤害效应，并伴有脊髓小胶质细胞M1表型抑制和M2表型上调，同时观察到炎症反应减轻。这些结果表明，脊髓中小胶质细胞向M1表型的不平衡极化可能有助于骨癌疼痛的发展，而脱氢皮质醇有助于减轻骨癌疼痛，脊髓中小胶质细胞向M2表型极化。
Bone cancer pain remains a major challenge in patients with primary or metastatic bone cancer due to a lack of understanding the mechanisms. Previous studies have revealed the two distinct functional polarization states of microglia (classically activated M1 and alternatively activated M2) in the spinal cord in nerve injury–induced neuropathic pain. However, whether microglia in the spinal cord polarize to M1 and M2 phenotypes and contribute to the development of bone cancer pain remains unclear. In this study, we used a mouse model with bone cancer to characterize the M1/M2 polarization of microglia in the spinal cord during the development of bone cancer pain, and investigated the antinociceptive effects of dehydrocorydaline, an alkaloidal component isolated from Rhizoma corydalis on bone cancer pain. Our results show that microglia in the spinal cord presented increased M1 polarization and decreased M2 polarization, while overproduction of IL-1β and inhibited expression of IL-10 was detected during bone cancer pain development. Intraperitoneal administration of dehydrocorydaline (10 mg/kg) had significant antinociceptive effects on day 14 after osteosarcoma cell implantation, accompanied by suppressed M1 phenotype and upregulated M2 phenotype of microglia in the spinal cord, while alleviated inflammatory response was observed then. These results suggest that the imbalanced polarization of microglia toward the M1 phenotype in the spinal cord may contribute to the development of bone cancer pain, while dehydrocorydaline helps to attenuate bone cancer pain, with microglial polarization shifting toward the M2 phenotype in the spinal cord.
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影响因子：
15.1
作者：
Li, Zhilin;Wei, Hong;Tian, Li
通讯作者：
Tian, Li
强烈的脊髓神经炎症介导 Walker 256 诱导的骨癌大鼠的机械异常性疼痛
影响因子：
3.6
作者：
Mao-Ying QL;Wang XW;Yang CJ;Li X;Mi WL;Wu GC;Wang YQ
通讯作者：
Wang YQ
DOI：
10.1523/jneurosci.3257-09.2009
发表时间：
2009-10-28
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Kigerl KA;Gensel JC;Ankeny DP;Alexander JK;Donnelly DJ;Popovich PG
通讯作者：
Popovich PG
雷公藤甲素通过抑制脊髓胶质细胞HDACs上调对骨癌疼痛大鼠的镇痛作用
影响因子：
9.3
作者：
Hu XF;He XT;Zhou KX;Zhang C;Zhao WJ;Zhang T;Li JL;Deng JP;Dong YL
通讯作者：
Dong YL
影响因子：
4.2
作者：
Chatzipanteli, K;Garcia, R;Dietrich, WD
通讯作者：
Dietrich, WD