槐定碱对骨癌痛小鼠的影响及其作用机制

目的 探讨槐定碱在骨癌痛小鼠中的影响及其作用机制。方法 将24只C57BL/6小鼠随机分成假手术组（Sham 组）、骨癌痛组（BCP 组）、骨癌痛+生理盐水组（BCP+NS组）、骨癌痛+槐定碱组（BCP+Sophoridine组，25 mg/kg）。分别于癌细胞接种前1 d以及接种后3 d、5 d、7 d、10 d和14 d时检测机械缩足阈值和热痛阈值；Western blot法检测脊髓L4⁃L5段背根神经节和大脑皮层组织中DAP12/Trem2/TLR4轴相关蛋白的表达水平。结果 与Sham组相比，在术后5 d、7 d、10 d、14 d，BCP组机械缩足阈值及热痛阈值均明显降低（均P<0.05）。与BCP组相比，在术后5 d、7 d、10 d、14 d，BCP+Sophoridine组的热痛阈值均明显升高（均P<0.05）；术后10 d、14 d，BCP+Sophoridine组机械缩足阈值均明显升高（均P<0.05）。Western blot实验结果显示，与BCP组相比，BCP+Sophoridine组小鼠背根神经节和大脑皮层组织中的TLR4蛋白表达水平均显著减少（均P<0.05），DAP12、Trem2蛋白表达水平均显著升高（均P<0.05）。结论 槐定碱可减轻骨癌痛小鼠癌痛行为，其机制可能与调控DAP12/Trem2/TLR4轴有关。

Effect of Sophoridine in mice with bone cancer pain and its mechanism

Objective To investigate the effect of Sophoridine in mice with bone cancer pain (BCP) and its mechanism. Methods A total of 24 C57BL/6 mice were randomly divided into sham surgery group (Sham group), bone cancer pain group (BCP group), bone cancer pain+normal saline group (BCP+NS group), and bone cancer pain+Sophoridine group (BCP+Sophoridine group, 25 mg/kg). The mechanical paw withdrawal threshold and the paw withdrawal latency were detected at 1 d before and 3 d, 5 d, 7 d, 10 d and 14 d after cancer cell inoculation. The expression levels of dorsal root ganglion of spinal cord L4⁃L5 segment and DAP12/Trem2/TLR4 axis⁃related proteins in the cerebral cortex tissues were determined by Western blot. Results Compared with the Sham group, the mechanical paw withdrawal threshold and the paw withdrawal latency in the BCP group were significantly reduced at 5 d, 7 d, 10 d and 14 d after surgery (all P<0.05).Compared with the BCP group, the paw withdrawal latency in the BCP+Sophoridine group was significantly increased at 5 d, 7 d, 10 d, and 14 d after surgery (all P<0.05), while the mechanical paw withdrawal threshold was significantly increased in the BCP+Sophoridine group at 10 d and 14 d after surgery (all P<0.05). Western blot results showed that compared with the BCP group, the protein expressions of TLR4 in both dorsal root ganglion and cerebral cortex tissues of mice in the BCP+Sophoridine group were significantly reduced (all P<0.05), and the protein expressions of DAP12 and Trem2 were significantly increased (all P<0.05). Conclusions Sophoridine can alleviate bone cancer pain, and the underlying mechanism may be related to the DAP12/Trem2/TLR4 axis.