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目的:观察附子-白术药对抑制裸鼠乳腺癌骨转移骨损伤作用,并探讨其作用机理。方法:左心室注射MDA-MB-231BO细胞法建立乳腺癌骨转移裸鼠模型;分别采用生理盐水、附子-白术药对、唑来膦酸进行干预;观察裸鼠模型的骨转移组织病理变化,TRACP染色进行破骨细胞计数,ELISA法测定骨转移组织中细胞因子TNF-α、IL6、IL-8和IL-4含量,Western-blot检测骨转移组织中NF-κB p65蛋白的表达。结果:附子-白术药对组、唑来膦酸组骨转移组织病理损伤较模型组减轻;与模型组比较,附子-白术药对组裸鼠骨转移灶中TRACP(+)细胞数量明显减少(P<0.01),骨转移组织中TNF-α、IL6和IL-8均显著降低(P<0.05,P<0.01),IL-4含量显著升高(P<0.05),NF-κB p65表达均显著降低(P<0.01)。结论:附子-白术药对抑制了乳腺癌骨转移裸鼠模型骨损伤,其机理可能与其抑制NF-κB通路活化,进而减少促炎因子TNF-α、IL6和IL-8等的分泌,并上调抑炎因子IL-4有关。
Objective: To observe the effect of aconite and atractylodes rhizome on inhibition of bone metastasis of breast cancer with bone metastasis in nude mice and its mechanism of action. Methods: MDA-MB-231BO cells were injected into the left ventricle to establish a model of breast cancer bone metastasis in nude mice. Physiological saline, aconite-Atractylodes and zoledronic acid were used respectively to observe the pathological changes of bone metastases in nude mice. The counts of osteoclasts were counted by TRACP staining. The levels of TNF-α, IL-6, IL-8 and IL-4 were measured by ELISA. The expression of NF-κB p65 in bone metastasis was detected by Western-blot. Results: Compared with the model group, the number of TRACP (+) cells in the bone metastases of the aconite-Atractylodes macrocephala group and the zoledronic acid group was significantly reduced compared with the model group P <0.01). The levels of TNF-α, IL6 and IL-8 in bone metastases were significantly decreased (P <0.05, P <0.01) Significantly lower (P <0.01). Conclusion: Aconite - Atractylodes rhizome inhibits the bone injury in nude mice with bone metastasis of breast cancer, which may be related to the inhibition of NF-κB pathway activation and the decrease of the secretion of proinflammatory cytokines such as TNF-α, IL6 and IL-8 Anti-inflammatory cytokine IL-4-related.