【摘要】 目的 探讨芋螺多肽AuIB在骨癌痛小鼠中的镇痛作用及其可能的作用机制。方法 将36只C57BL/6小鼠随机分成假手术组(SHAM组）、骨癌痛组(BCP组）、生理盐水对照组(NS组）、低剂量（0.6 mg/kg）AuIB给药组(AuIB1组）、中剂量（1.2 mg/kg）AuIB给药组（AuIB2组）和高剂量（2.4 mg/kg）AuIB给药组（AuIB3组）。术后第14天利用X影像和HE染色观察小鼠股骨病理学变化情况；分别于癌细胞接种前1 d以及接种后3 d、5 d、7 d、11 d和14 d时检测机械缩足阈值；Western blot法检测脊髓L4-L5段背根神经节和大脑皮层组织中PI3K/AKT信号通路相关蛋白的表达水平。结果 与SHAM组相比，术后14 d BCP组的X影像提示骨质破坏，HE染色提示癌细胞浸润；与SHAM组相比，术后第7天起BCP组的机械缩足阈值明显降低（P<0.05）；与BCP组相比，AuIB1组、AuIB2组和AuIB3组分别在术后第14 d、11 d和7 d出现机械缩足阈值明显升高（均P<0.05）；与BCP组相比，AuIB3组背根神经节和大脑皮层组织p-PI3K/PI3K、p-AKT/AKT比例显著减少（均P<0.05）。结论 芋螺多肽AuIB可减轻骨癌痛小鼠的机械痛行为，作用机制可能与抑制PI3K/AKT信号通路有关。更多还原

【Abstract】 Objective To investigate the analgesic effect and possible mechanism of α-Conotoxin AuIB on the bone cancer pain of mice.Methods A total of 36 C57 BL/6 mice were randomly divided into a SHAM operation group(SHAM group), a bone cancer pain group(BCP group), a normal saline control group(NS group), a low dose(0.6 mg/kg) AuIB group(AuIB1 group), a medium dose(1.2 mg/kg)AuIB group(AuIB2 group) and a high dose(2.4 mg/kg) AuIB group(AuIB3 group). The pathological changes of mouse femur were observed by X-ray and HE staining on the 14 th day after operation. The mechanical paw withdrawal threshold was detected 1 day before and 3, 5, 7, 11 and 14 days after inoculation. The expression of PI3 K/p-AKT signaling pothway-related proteins in L4-L5 dorsal root ganglion and cerebral cortex tissues was detected by Western blot.Results Compared with the SHAM group, the X-ray of the BCP group 14 days after surgery indicated bone destruction and HE staining indicated infiltration of cancer cells. Compared with the SHAM group, the mechanical paw withdrawal threshold of the BCP group decreased significantly from the 7 th day after surgery(all P<0.05).Compared with the BCP group, the mechanical paw withdrawal threshold of AuIB1 group, AuIB2 group, and AuIB3 group were significantly increased on the 14 th, 11 th, 7 th days after surgery(all P<0.05). Compared with BCP group, the proportion of p-PI3 K/PI3 K and p-AKT/AKT in dorsal root ganglion and cerebral cortex tissues of the AuIB3 group decreased significantly(all P<0.05).Conclusions The α-Conotoxin AuIB can reduce the bone cancer pain of mice, and its mechanism may be related to the inhibition of PI3 K/AKT signaling pathway.更多还原