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鞘内注射白藜芦醇对骨癌痛模型大鼠痛觉及OPG/RANK/RANK-L信号通路的影响
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| 篇名： | 鞘内注射白藜芦醇对骨癌痛模型大鼠痛觉及OPG/RANK/RANK-L信号通路的影响 |
| TITLE： | Effects of intrathecal injection of resveratrol on sense of pain and OPG/RANK/RANK-L signal pathway in rats with bone cancer pain |
| 摘要： | 目的 研究鞘内注射白藜芦醇对骨癌痛模型大鼠痛觉及骨保护素（OPG）/核因子κB受体激活因子（RANK）/RANK配体（RANK-L）信号通路的影响。方法将经鞘内置管处理后的大鼠分为假手术组、模型组和白藜芦醇低、中、高剂量组（0.25、1、2mg/kg），每组8只。除假手术组外，其余各组大鼠右后肢胫骨注射乳腺癌Walker256细胞悬液以复制骨癌痛模型。造模12d后，白藜芦醇各剂量组大鼠鞘内注射相应药物，模型组和假手术组大鼠注射等体积二甲基亚砜，注射量为10μL，每天1次，连续5d。检测大鼠给药后第3、5天的机械缩足反射阈值和热缩足反射潜伏期。检测大鼠末次给药后血清中肿瘤坏死因子α（TNF-α）、白细胞介素6（IL-6）、IL-1β、趋化因子配体2（CCL2）水平，以及胫骨中RANK、RANK-L、OPG蛋白表达水平。结果术后第12天，与假手术组相比，模型组大鼠机械缩足反射阈值、热缩足反射潜伏期均显著降低（P＜0.05）。给药后第3、5天，与模型组相比，白藜芦醇中、高剂量组大鼠机械缩足反射阈值、热缩足反射潜伏期均显著升高（P＜0.05）。给药后第5天，与模型组相比，白藜芦醇中、高剂量组大鼠血清中TNF-α、IL-6、IL-1β、CCL2水平均显著降低（P＜0.05）；白藜芦醇低剂量组大鼠血清中IL-6水平显著降低（P＜0.05）；白藜芦醇中剂量组大鼠胫骨中RANK、RANK-L蛋白表达水平均显著降低，OPG蛋白表达水平显著升高（P＜0.05）。结论鞘内注射白藜芦醇可缓解大鼠骨癌痛引起的炎症反应，其作用机制可能与抑制OPG/RANK/RANK-L信号通路活性有关。 |
| ABSTRACT： | OBJECTIVE To study the effects of intrathecal injection of resveratrol on sense of pain and OPG/RANK/RANK-L signal pathway in rats with bone cancer pain. METHODS After treatment via intrathecal tube ，the rats were randomly divided into sham operation group ，model group ，resveratrol low-dose ，medium-dose and high-dose groups （0.25，1，2 mg/kg），with 8 rats in each group. Except for sham operation group ，other groups were given Walker 256 breast cancer cell suspension on the right hind limb tibia to induce bone cancer pain model. After 12 days of modeling ，intrathecal administration was performed in resveratrol groups. The model group and sham operation group received the same volume of dimethyl sulfoxide ，10 μL，once a day ，for 5 days. The paw withdrawal mechanical threshold （PWMT）and paw withdrawal thermal latency （PWTL）were measured at 3 d，5 d after administration. The serum levels of tumor necrosis factor α（TNF-α），interleukin 6（IL-6），IL-1β and chemokine ligand 2 （CCL2）were determined after last medication ，and the protein expressions of RANK ，RANK-L and OPG in tibia were also determined. RESULTS Compared with sham operation group ，PWMT and PWTL were significantly decreased in the model group 12 days after operation （P＜0.05）. Compared with model group ，PWMT and PWTL were significantly increased in resveratrol medium-dose and high-dose groups at 3 d and 5 d after administration （P＜0.05）. Compared with model group ，the levels of TNF-α，IL-6，IL-1β and CCL2 in serum were significantly decreased in resveratrol middle-dose and high-dose groups at 5 d after administration（P＜0.05）；the expression of IL- 6 in serum was significantly decreased in resveratrol low-dose group （P＜0.05）； the protein expressions of RANK-L and RANK in tibia were significantly decreased ，while the protein expression of OPG was increased significantly in resveratrol middle-dose group （P＜0.05）. CONCLUSIONS Resveratrol by intrathecal injection can relieve the inflammation caused by bone cancer pain of rats ， the mechanism of which may be associated with inhibiting the activity of OPG/RANK/RANK-L signal pathway. |
| 期刊： | 2022年第33卷第13期 |
| 作者： | 周芳，林涛，代月娥，周勤，蒋蓉 |
| AUTHORS： | ZHOU Fang，LIN Tao，DAI Yue ’e，ZHOU Qin，JIANG Rong |
| 关键字： | 骨癌痛；白藜芦醇；OPG/RANK/RANK-L信号通路；镇痛 |
| KEYWORDS： | bone cancer pain ；resveratrol；OPG/RANK/ |
| 阅读数： | 186 次 |
| 本月下载数： | 4 次 |
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