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目的探讨阳和汤对阳虚证乳腺癌骨转移裸鼠模型的影响及其相关机制。方法将70只裸鼠随机分为空白对照组(NS组),阳虚骨转移组(YG组),阳虚骨转移+唑来膦酸组(YGZ组),阳虚骨转移+阳和汤等临床剂量组(YGY组),阳虚骨转移+阳和汤2倍临床剂量组(YG2Y组),骨转移+唑来膦酸组(GZ组),骨转移+阳和汤等临床剂量组(GY组)7组。肌注氢化可的松建立阳虚证裸鼠模型;再将NS组以外的所有裸鼠左心室注射乳腺癌细胞MDA-MB-231悬液建立裸鼠骨转移模型;YGY、YG2Y、GY组造模后第5天开始中药煎剂灌胃干预,YGZ、GZ组于造模后第5、7、9、12、14、16、19天腹腔注射唑来膦酸,YG组造模1周后灌胃蒸馏水。用药20天后对裸鼠进行X线摄像、影像学评分、病理组织观察,取骨转移组织进行RT-PCR和Western-blot检测骨保护素(osteoprotegerin,OPG)、核因子κB受体活化因子配体(receptor activator of nuclear factor-κB ligand,RANKL)的基因及蛋白表达量。结果阳和汤能在一定程度上改善裸鼠模型的生存质量(P<0.05),抑制骨转移,治疗骨转移引起的溶骨性骨质破坏(P<0.05),并能明显增加裸鼠OPG的表达(P<0.01)、抑制RANKL的表达(P<0.01)。结论阳和汤等临床剂量能有效治疗阳虚证乳腺癌骨转移,其可能机制是通过增加OPG的表达、抑制RANKL的表达,从而抑制乳腺癌骨转移的发展。
Objective To investigate the effect of Yanghe decoction on the model of bone metastasis in nude mice with Yang Deficiency Syndrome and its related mechanism. Methods Seventy nude mice were randomly divided into blank control group (NS group), yang bone metastasis group (YG group), yang bone metastasis + zoledronic acid group (YGZ group), yang bone metastasis (YGY group), Yang xiang bone metastasis + Yanghe decoction 2 times clinical dose group (YG2Y group), bone metastasis + Zoledronic acid group (GZ group), bone metastasis + Yanghe decoction and other clinical dose groups (GY group) 7 groups. Mice were injected intramuscularly with hydrocortisone to establish a model of Yang deficiency syndrome in nude mice. All the mice except the NS group were injected with MDA-MB-231 suspension into the left ventricle to establish the model of bone metastasis in nude mice. The model of YGY, YG2Y and GY On the fifth day after the model was started, the decoction of Chinese herbs was intragastrically administered. In the YGZ and GZ groups, zoledronic acid was injected intraperitoneally on the 5th, 7th, 9th, 12th, 14th, Gavage with distilled water. Twenty days after treatment, the nude mice were examined by X-ray, imaging and histopathology. The bone metastasis tissues were taken for detection of osteoprotegerin (OPG), nuclear factor kappa B receptor activator ligand (receptor activator of nuclear factor-κB ligand, RANKL) gene and protein expression. Results Yanghe decoction could improve the quality of life in nude mice to a certain extent (P <0.05), inhibit bone metastasis and treat osteolytic bone destruction caused by bone metastasis (P <0.05), and significantly increase the expression of OPG (P <0.01), and inhibited the expression of RANKL (P <0.01). Conclusions Yanghe Decoction and other clinical doses can effectively treat bone metastasis of breast cancer of Yang-deficiency syndrome. Its possible mechanism is to inhibit the development of bone metastasis of breast cancer by increasing the expression of OPG and inhibiting the expression of RANKL.