摘要
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 explore the influence of Yanghe Decoction on bone metastasis of breast cancer nude mice model with yang deficiency syndrome and the related mechanism. Methods 70 nude mice were randomly divided into 7 groups： the blank group（ NS group）,yang deficiency of bone metastasis group（ YG group）,yang deficiency of bone metastasis ＋ zoledronic acid group（ YGZ group）,yang deficiency of bone metastasis ＋ clinical dose of Yanghe Decoction group（ YGY group）,yang deficiency of bone metastasis ＋ 2 times clinical dose of Yanghe Decoction group（ YG2 Y group）,bone metastasis ＋ zoledronic acid group（ GZ group）,bone metastasis ＋ clinical dose of Yanghe Decoction group（ GY group）. The yang deficiency groups were intramuscularly injected hydrocortisone to establish the nude mice model of yang deficiency syndrome,the nude mice model with bone metastasis of breast cancer was established by injecting breast cancer cells of MDA-MB-231 cell suspension into the left cardiac ventricle of the mice except the blank group. The groups of YGY,YG2 Y,GY were given decoction of Chinese herbal medicines by gastric infusion which started from the fifth day after modeling,the positive control groups were given peritoneal injection with zoledronic acid on the day 5,7,9,12,14,16,19 after modeling,YG group administered with distilled water by gastrogavage for one week after modeling. After 20 days,X-ray photograph,image scores,pathological tissue observation were conducted in the nude mice,the metastatic foci in bone were removed to determine the gene and protein expression level of OPG,RANKL by PT-PCR and Western-blot. Results Yanghe Decoction could improve the quality of nude mice’ life to a certain extent（ P 〈 0. 05）,inhibit bone metastasis,treat osteolytic bone destruction brought about by bone metastasis（ P 〈 0. 05）,and it could also increase the expression of OPG（ P 〈 0. 01）,inhibit the expression of RANKL（ P 〈 0. 01）. Conclusion Yanghe Decoction with the clinical dose cou
出处
《北京中医药》
2017年第1期27-32,共6页
Beijing Journal of Traditional Chinese Medicine
基金
高等学校博士学科点专项科研基金项目(2011432311006)
湖南省自然科学基金项目(12JJ5055)
关键词
RANK
RANKL
OPG
阳和汤
乳腺癌骨转移
中医证候
阳虚证
RANK
RANKL
OPG
Yanghe Decotion
bone metastasis of breast cancer
TCM syndrome
yang deficiency syndrome
