目的 探讨白术附子汤抑制乳腺癌骨转移裸鼠模型骨损伤的作用机理。方法 建立乳腺癌骨转移裸鼠模型，用白术附子汤组、附子-白术药对进行干预，观察裸鼠模型的生存时间，用抗酒石酸酸性磷酸酶(TRACP)染色进行破骨细胞计数，RT-PCR法检测乳腺癌骨转移组织中巨噬细胞集落刺激因子(M-CSF)、甲状旁腺激素相关肽(PTHrP)基因的表达，Western blot检测骨转移组织中M-CSF、PTHrP蛋白的表达。结果 与模型组比较，附子-白术药对组、白术附子汤组生存时间显著延长(P ＜ 0.01)；附子-白术药对组、白术附子汤组裸鼠骨转移灶中TRACP阳性细胞数量明显减少(P < 0.01)；附子-白术药对组、白术附子汤组M-CSF mRNA、PTHrP mRNA的相对表达量显著降低(P < 0.01)；附子-白术药对组、白术附子汤组M-CSF、PTHrP蛋白相对表达量显著降低(P < 0.01)；白术附子汤组M-CSF、PTHrP蛋白相对表达量有低于附子-白术药对组的趋势。结论 白术附子汤抑制乳腺癌骨转移裸鼠模型骨损伤的作用与其下调乳腺癌骨转移组织中骨破坏因子M-CSF、PTHrP基因和蛋白的表达有关；附子-白术药对与白术附子汤功效相近，可能是白术附子汤的核心药物。

Objective To investigate the inhibitory mechanism of Baizhu Fuzi Decoction(BFD) on bone damage of nude mice model with bone metastases of breast cancer. Methods The nude mice model with bone metastases of breast cancer was established，and then the modeled mice were treated with BFD and drug pair of Radix Aconite Preparata(Fuzi) and Rhizoma Atractylodis Macrocephalae(Baizhu)，respectively. After treatment，the survival time of nude mice was observed，the count of osteoclast was detected after tartrate-resistant acid phosphatase(TRACP)staining，the gene expression of macrophage colony stimulating factor(M-CSF) and parathyroid hormone related peptide(PTHrP) in the bone metastases of breast cancer was examined by the RT-PCR and their protein expression was detected by Western blot method. Results Compared with the model group，the survival time was obviously prolonged(P＜0.01)，the amount of TRACP positive cells in the bone metastases of breast cancer was reduced(P < 0.01)，M-CSF and PTHrP mRNA relative expression levels as well as their protein relative expression levels were decreased obviously(P < 0.01) in BFD group and Fuzi-Baizhu drug pair group. And BFD group showed better effect on decreasing M-CSF and PTHrP protein expression levels than Fuzi-Baizhu drug pair group，but the difference was not statistically significant(P > 0.05). Conclusion BFD shows certain effect on relieving bone damage in nude mice model with bone metastases of breast cancer，and its mechanism is probably related with the down-regulation of gene and protein expression of osteoclasia factors of M-CSF and PTHrP in the bone metastases of breast cancer. The therapeutic effect of Fuzi-Baizhu drug pair is similar to that of BFD，indicating that Fuzi-Baizhu drug pair is the core drug of BFD.

R285.5

河南省科技厅科技攻关项目(112102310108)；河南省科技厅基础与前沿项目(102300410040)；河南省教育厅科技攻关计划(2010B360005)；郑州市金水区科技攻关项目(20093542)。