摘要
目的:从调节护骨素(OPG)/细胞核因子κB受体活化因子配体(RANKL)系统探讨附子白术汤抑制乳腺癌骨转移骨损伤的机制。方法:采用左心室注射人乳腺癌骨转移细胞株(MDA-MB-231BO)细胞法建立乳腺癌骨转移裸鼠模型;随机分为模型组、唑来膦酸组、附子白术汤组、附子-白术药对组,另备正常裸鼠正常组(n=6)。造模后第4天开始药物干预:唑来膦酸组sc唑来膦酸0.2 mg.kg-1;模型组、附子白术汤组、附子-白术药对组、正常组,分别ig给予生理盐水20 mL.kg-1、附子白术汤5.6 g.kg-1、附子-白术药对煎液2.4 g.kg-1、生理盐水20 mL.kg-1;每周3次,持续6周。观察各组裸鼠体重、骨转移灶病理和OPG,RANKLmRNA表达变化。结果:①与模型组比较,附子-白术药对组与附子白术汤组骨转移个数、骨转移率及体重下降率均明显下降(P<0.05),骨转移灶中TRAP(+)细胞数量均减少(P<0.01),OPG mRNA表达含量上调(P<0.01),RANKLmRNA表达含量及二者比值降低(P<0.01);②与附子白术汤组比较,附子-白术药对组骨转移个数、骨转移率、体重下降率、骨转移灶中TRAP细胞数量,OPG mRNA,RANKL mRNA表达含量及其比值均无统计学差异。结论:附子白术汤和附子-白术药对均可通过调节OPG/RANKL系统,减少破骨细胞的数量并抑制其活性,从而减轻乳腺癌骨转移裸鼠溶骨性损伤;附子-白术药对与附子白术汤功效相近,可能是附子白术汤的核心药物。
Objective： To explore the mechanism of inhibiting the bone injury by Fuzi Baizhu decoction in bone metastases of breast cancer by regulating osteoprotegerin（OPG）/receptor activator of nuclear-κB ligand（RANKL）.Method： The model of breast cancer bone metastases was established by injecting the MDA-MB231BO cells into left ventricle.24 nude mice in model group were divided into model group,zoledronic acid group,Fuzi Baizhu decoction group and rhizoma atractylodis macrocephalae-radix aconiti carmichaeli group randomly,and another 6 normal unde mice were as normal group（n = 6）.Four days after the modeling,the drug intervention was carried out respectively： zoledronic acid group was treated with,zoledronic acid,0.2 mg.kg-1;model group,rhizoma atractylodis macrocephalaeradix aconiti carmichaeli decoction group,rhizoma atractylodis macrocephalae-radix aconiti carmichaeli group and normal group： normal sodium（NS） 20 mL.kg-1,Fuzi Baizhu decoction 5.6 g.kg-1,rhizoma atractylodis macrocephalae-radix aconiti carmichaeli 2.4 g.kg-1 and NS 20 mL.kg-1 merely,po;3 times every week,lasting 6 weeks.The weight,pathology of bone metastases focus were observed and OPG mRNA and RANKLmRNA expression was detected.Result： ①In the model group,the number and rate of bone metastases and weight loss of the pair of rhizoma atractylodis macrocephalae and radix aconiti carmichaeli group and Fuzi Baizhu decoction group declined obviously（P 0.05）,the number of TRAP（＋） reduced in the bone metastases（P 0.01）,the OPGmRNA relative expression content increased（P 0.01）,the RANKLmRNA relative expression content and ratio declined obviously（P 0.01）;② In the group of the Fuzi Baizhu decoction,the number and the rate of bone metastases,the rate of weight loss,the number of TRAP（＋）,the OPGm RNA and the RANKL mRNA relative expression content and ratio had no statistically significant differences between rhizoma atractylodis macrocephalae and radix aconiti carmichaeli group.Conclusion： Both decoction of rhizoma atractylodis macrocephalae and radix aconiti carmichaeli and the pair of Rhizoma Atractylodis Macrocephalae and radix aconiti carmichaeli could regulate OPG / RANKL,decrease osteoclast and restrain activity of them,reduce osteolytic damage accordingly.
出处
《中国实验方剂学杂志》
CAS
北大核心
2013年第15期206-210,共5页
Chinese Journal of Experimental Traditional Medical Formulae
基金
河南省科技厅2011年科技攻关项目(112102310108)
河南省科技厅2010年基础与前沿项目(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)
