药对“蛇床子-补骨脂”与乳腺癌骨转移裸鼠体重变化与骨代谢的量效关系研究

Dose-effect Relationship of Chinese Medicines Cnidium Fruit-Psoralea Fruit in Pairs on the Body Weight and Bone Metabolism of Mammary Cancer Bone Metastasis in Nude Mice

目的从调节破骨细胞分化的主要途径护骨素(OPG)/细胞核因子κB受体活化因子配体(RANKL)/细胞核因子κB受体活化因子(RANK)系统研究蛇床子-补骨脂温肾药对抑制乳腺癌骨转移的作用机制。方法将42只乳腺癌骨转移裸鼠随机分为模型组、唑来磷酸组、蛇床子组、补骨脂组、2:2配比组、1:3配比组、3:1配比组,每组6只;另备正常裸鼠6只作为正常组。分别给予相应的药液灌胃,唑来磷酸组皮下注射,正常组给予生理盐水灌胃,持续6周。观察裸鼠的体重、骨转移灶病理和OPG、RANKL mRNA表达水平变化。结果 3:1配比组和2:2配比组体重下降率明显低于其他配比组,而2:2配比组低于3:1配比组;不同比例配伍组的骨抗酒石酸酸性磷酶(TRAP)(+)细胞数差异均有统计学意义,2:2配比组优于1:3配比组(P<0.05);不同配比的蛇床子-补骨脂可不同程度地上调OPG基因表达,下调RANKL基因表达,从基因方面调节OPG/RANKL的分泌比例,其中2:2配比组的疗效优于其他配比组。结论不同配比的蛇床子-补骨脂均具有一定的抑制乳腺癌骨转移作用,其中2:2配比组疗效最突出,其作用机制可能是调节了OPG/RANKL基因分泌比例。

Objective To study the mechanism of inhibiting mammary cancer bone metastasis of the warming kidney medi- cines Shechuangzi （Fructus Cnidii） - Buguzhi （Fructus Psoraleae） from the OPG/RANKL/RANK system of regulating osteo- clast differentiation. Methods The 42 successfully made nude mice models with mammary cancer bone metastasis were ran domized into model group, zoledronic acid group, Cnidium group, Psoralea group, 2 ： 2 ratio group, 1 = 3 ratio group, and 3 ： 1 ratio group, with 6 in each. The other 6 normal nude mice were taken as a normal group. They were given the corresponding liquid medicine by gavage respectively, but the zoledronic acid group was given intraperitoneal injection, and the normal group was given normal saline by gavage, for 6 weeks. The changes of body weight, pathological manifestations of bone metastases focus, and expression of osteoprotegerin and receptor activator of nuclear factor-kappa B ligand mRNA of nude mice were ob served. Results The weight loss rate of the 3 ： 1 group and 2 ： 2 groups were significantly lower than other compatible groups, and that of the 2 ： 2 group was lower than of the 3 ： 1 group. The amount of bone TRACP （＋） cells of different com- patible groups was all statistically different, and the 2 ： 2 group was superior to other compatible groups. The different com patibility of Shechuangzi （Fructus Cnidii） and Buguzhi （Fructus Psoraleae） could up-regulate the OPG expression to different degrees and down regulate the RANKL expression, thus it was regulating the OPG/RANKL secretion ratio from the gene lev- el. The effect of 2 ： 2 group was better than other compatible groups in result. Conclusion All different compatibilities of Shechuangzi （Fructus Cnidii） and Buguzhi （Fructus Psoraleae） have inhibition effect on mammary cancer bone metastasis, while the effect of 2 ： 2 group is the most superior. Its possible mechanism is probably related with the regulation of OPG/ RANKL secretion ratio.