Page 82 - 《中国药房》2022年13期

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 Δ

1
周 芳 ，林 涛 ，代月娥 ，周 勤 ，蒋 蓉 （1.四川省医学科学院/四川省人民医院麻醉科，成都 610072；
2
1＊
2
1 #
2.四川省医学科学院/四川省人民医院疼痛科，成都 610072）
中图分类号 R965 文献标志码 A 文章编号 1001-0408（2022）13-1612-05
DOI 10.6039/j.issn.1001-0408.2022.13.13

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、2 mg/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12 d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10 μL，每天1次，连续5 d。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。
关键词 骨癌痛；白藜芦醇；OPG/RANK/RANK-L信号通路；镇痛

Effects of intrathecal injection of resveratrol on sense of pain and OPG/RANK/RANK-L signal pathway in
rats with bone cancer pain
2
1
1
2
ZHOU Fang ，LIN Tao ，DAI Yue’e ，ZHOU Qin ，JIANG Rong（1. Dept. of Anesthesiology，Sichuan Academy of
1
Medical Sciences/Sichuan Provincial People’s Hospital，Chengdu 610072，China；2. Dept. of Pain Medicine，
Sichuan Academy of Medical Sciences/Sichuan Provincial People’s Hospital，Chengdu 610072，China）
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 Walker256 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，
Δ 基金项目 四川省科技计划（重点研发）项目（No.2022YFS0278）
the mechanism of which may be associated with inhibiting the
＊第一作者 主治医师，硕士。研究方向：麻醉与疼痛。E-mail：
258625523@qq.com activity of OPG/RANK/RANK-L signal pathway.
# 通信作者 主治医师，硕士。研究方向：脑外科麻醉和疼痛管 KEYWORDS bone cancer pain；resveratrol；OPG/RANK/
理。E-mail：anthea_365@163.com RANK-L signal pathway；analgesia

·1612 · China Pharmacy 2022 Vol. 33 No. 13 中国药房 2022年第33卷第13期