Objective To study the influences of coupled medicinal-Shechuangzi (Fructus Cnidii) and Buguzhi {Fructus Psorakae) on survival time, activity of osteoclast and bone injury in nude mice with breast cancer with bone metastasis, and discuss the best combination of the coupled medicinal in the treatment of breast cancer with bone metastasis. Methods The model of nude mouse was established by using left ventricle injection of MDA-MB-231BO cells. The effect of coupled medicinal-Shechuangzi and Buguzhi(2. 56 g/mouse) was observed taking zoledronic acid as a positive control medicinal. All nude mice (n =84) were randomly divided into(0.2 mg/kg) group A and group B (each n =42), and each group were randomly divided again into model group, zoledronic acid group, 4 parts Shechuangzi to 0 part Buguzhi group (4 to 0 group) , 0 part Shechuangzi to 4 parts Buguzhi group (0 to 4 group) , 1 part Shechuangzi to 3 parts Buguzhi group (1 to 3 group), 2 parts Shechuangzi to 2 parts Buguzhi group (2 to 2 group), 3 parts Shechuangzi to 1 parts Buguzhi group (3 to 1 group, each re =6). A normal group (n = 6) was additionally set into group B. The survival time was observed in group A after intervention by different proportions of medicinal. The samples were collected 6 weeks after intervention by different proportions of medicinal in group B. The changes of morphology and quantity of osteoclasts were observed after TRACP staining, and the expressions of genes and proteins of M-CSF and PTHrP were detected in bone metastasis focus. Results The survival time was significantly prolonged in all intervention groups in nude mouse model (P <0. 05, P <0. 01), and the effect was the best in 2 to 2 group, which was almost as the same as that in zoledronic acid group. The activity of osteoclasts was inhibited to some extent in all intervention groups (P < 0. 05, P < 0. 01 ) , and the effect was the best in 2 to 2 group, which was almost as the same as that in zoledronic acid group. The expressions of genes and proteins of M-CSF and PTHrP were down-regulated to some extent in all intervention groups (P <0. 05, P <0.01) , and the effect was the best in 2 to 2 group. Conclusion The coupled medicinal-Shechuangzi and Buguzhi with the action of warming kidney can inhibit breast cancer with bone metastasis, and their proportion of two to two may be the best proportion with the best curative effect.%目的 研究药对蛇床子—补骨脂对裸鼠乳腺癌骨转移生存时间、破骨细胞活性及骨损伤的影响,探讨该药对治疗乳腺癌骨转移的最佳配伍关系.方法 用左心室注射MDA-MB-231BO细胞法对裸鼠进行造模,观察蛇床子—补骨脂药对(2.56 g/只)的作用,以唑来膦酸(0.2 mg/kg)作为阳性对照药.将84只裸鼠模型随机分为A、B组,每组42只,每组再随机分为模型组、唑来膦酸组和蛇床子—补骨脂4∶0、0∶4、1∶3、2∶2、3∶1组,每组6只,实验B组另配正常组裸鼠6只.实验A组观察不同配比药对干预后各组模型的生存时间；实验B组不同配比药对干预6周后取材,TRACP染色观察各组破骨细胞的形态和数量,检测骨转移灶M-CSF、PTHrP的基因与蛋白的表达.结果 各干预组均能显著延长裸鼠模型的生存时间(P＜0.05,P＜0.01),中药组以2∶2配伍最好,疗效接近唑来膦酸组；各干预组均可在一定程度上抑制乳腺癌骨转移裸鼠骨转移组织中破骨细胞的活性(P＜0.05,P＜0.01),中药组以2∶2配伍最好,疗效接近唑来膦酸组；各干预组均可不同程度地下调M-CSF、PTHrP的基因与蛋白的表达(P ＜0.05,P＜0.01),中药组以2∶2配伍最好.结论 基于温肾法的蛇床子—补骨脂药对可以抑制乳腺癌骨转移,该药对最佳疗效配伍比例可能是2∶2.
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