Hu Yahui, Kodithuwakku Nandani Darshika, Zhou Lin, Li Chengyuan, Han Dan, Fang Weirong, Liu Jihua, Li Yunman
State Key Laboratory of Natural Medicines, Department of Physiology, China Pharmaceutical University, Nanjing 210009, China.
Institute of Indigenous Medicine, University of Colombo, Rajagiriya 11600, Sri Lanka.
Molecules. 2017 Jun 6;22(6):937. doi: 10.3390/molecules22060937.
: Tumor compression-induced pain (TCIP) is a complex pathological cancer pain. Spinal glial cells play a critical role in maintenance of cancer pain by releasing proinflammatory cytokines and chemokines. In this study, we verified the role of -corydalmine (-CDL) on TCIP. : Spontaneous pain, paw withdrawal threshold and latency were assessed using TCIP mouse model. Immunofluorescence was used to identify the reactions of glia. RT-PCR and western blot or ELISA were used to determine mRNA or protein expression of tumor necrosis factor-α (TNF-α), interlukin-1β (IL-1β), CC chemokine ligand 2 (CCL2) and chemotactic cytokine receptor 2 (CCR2) in vivo and in vitro. : -CDL significantly attenuated TCIP hypersensitivity, accompanying with downregulation of TNF-α and IL-1β expression levels and declined astrocytes and microglial activation. It also significantly decreased the expression of the mRNA and protein level for CCL2 and CCR2. Further, -CDL could suppress TNF-α-induced astrocytes activation and IL-1β expression through downregulating the CCL2/CCR2. Besides, CCL2-induced BV-microglia activation and inflammatory factors secretion were suppressed by -CDL via CCR2. : Suppression of CCL2/CCR2 by -CDL may contribute to alleviate TCIP, offering an alternative medication for TCIP.
肿瘤压迫性疼痛（TCIP）是一种复杂的病理性癌痛。脊髓胶质细胞通过释放促炎细胞因子和趋化因子在维持癌痛中起关键作用。在本研究中，我们验证了紫堇碱（-CDL）对TCIP的作用。使用TCIP小鼠模型评估自发痛、爪部退缩阈值和潜伏期。采用免疫荧光法鉴定胶质细胞的反应。采用逆转录-聚合酶链反应（RT-PCR）、蛋白质印迹法或酶联免疫吸附测定（ELISA）在体内和体外测定肿瘤坏死因子-α（TNF-α）、白细胞介素-1β（IL-1β）、CC趋化因子配体2（CCL2）和趋化细胞因子受体2（CCR2）的mRNA或蛋白表达。-CDL显著减轻TCIP超敏反应，同时下调TNF-α和IL-1β表达水平，降低星形胶质细胞和小胶质细胞的活化。它还显著降低CCL2和CCR2的mRNA和蛋白水平表达。此外，-CDL可通过下调CCL2/CCR2抑制TNF-α诱导的星形胶质细胞活化和IL-1β表达。此外，-CDL通过CCR2抑制CCL2诱导的BV小胶质细胞活化和炎性因子分泌。-CDL对CCL2/CCR2的抑制作用可能有助于减轻TCIP，为TCIP提供了一种替代药物。
