六味地黄汤合三圣散联合唑来膦酸治疗前列腺癌骨转移的作用及机制研究  

Effect and mechanism of Liuwei Dihuang Decoction combined with Sansheng Powder and zoledronic acid on treatment of prostate cancer bone metastases

作　　者：张小青[1] 李禄[4] 王为民[1] 谢海波[1] 吴思[1] 邵荣江[1] 李庆[1] 杜学忠[1] 李洋洋 牟睿宇 贾春鑫 廖洋 李小江[2,3] ZHANG Xiao-qing;LI Lu;WANG Wei-min;XIE Hai-bo;WU Si;SHAO Rong-jiang;LI Qing;DU Xue-zhong;LI Yang-yang;MOU Rui-yu;JIA Chun-xin;LIAO Yang;LI Xiao-jiang(Department of Orthopedics,First Teaching Hospital of Tianjin University of Traditional Chinese Medicine,Tianjin 300193,China;Department of Oncology,First Teaching Hospital of Tianjin University of Traditional Chinese Medicine,Tianjin 300193,China;National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion,First Teaching Hospital of TianjinUniversity of Traditional Chinese Medicine,Tianjin 300381,China;Department of Acupuncture,Tianjin Nankai Hospital,Tianjin 300100,China)

机构地区：[1]天津中医药大学第一附属医院骨伤科,天津300381 [2]天津中医药大学第一附属医院肿瘤科,天津300381 [3]天津中医药大学第一附属医院国家中医针灸临床医学研究中心,天津300381 [4]天津市南开医院针灸科,天津300100

出　　处：《中草药》2022年第23期7461-7466,共6页Chinese Traditional and Herbal Drugs

基　　金：天津市中医药管理局中医中西医结合科研课题(2021106);天津市教委课题(2020KJ163);天津中医药大学第一附属医院拓新工程(院YB202125)。

摘　　要：目的 研究六味地黄汤合三圣散联合唑来膦酸治疗前列腺癌骨转移的作用及机制。方法 将前列腺癌骨转移小鼠随机分为模型组、六味地黄汤合三圣散组、唑来磷酸组和联合组,给予药物干预2周,采用ELISA法检测血清中碱性磷酸酶(alkaline phosphatase,ALP)活性;采用全自动生化分析仪检测血清中丙氨酸氨基转移酶(alanine aminotransferase,ALT)、天冬氨酸氨基转移酶(aspartate aminotransferase,AST)活性及尿肌酐(urine creatinine,CRE)、尿素氮(urine urea nitrogen,BUN)、血钙、血磷水平;采用Western blotting法检测股骨组织中p63、C-X-C基序趋化因子受体4(C-X-C motif chemokine receptor 4,CXCR4)和基质金属蛋白酶9(matrix metalloproteinase 9,MMP9)蛋白表达。结果 与模型组比较,六味地黄汤合三圣散与唑来膦酸联用显著降低小鼠血清中ALP、AST、ALT活性及CRE、BUN、血钙、血磷水平(P<0.05),显著上调股骨组织中p63表达(P<0.05),显著下调股骨组织中CXCR4和MMP9表达(P<0.05)。结论 六味地黄汤合三圣散联合唑来膦酸能够通过上调p63表达,抑制CXCR4和MMP9表达,从而延缓前列腺癌骨转移进程。Objective To study the effect and mechanism of Liuwei Dihuang Decoction(六味地黄汤) combined with Sansheng Powder(三圣散) and zoledronic acid in treatment of prostate cancer bone metastasis.Methods Mice with prostate cancer bone metastasis were randomly divided into model group,Liuwei Dihuang Decoction combined with Sansheng Powder group,zoledronic acid group and combination group.Mice were given drug intervention for 2 weeks,and alkaline phosphatase(ALP) activity in serum was detected by ELISA;Automatic biochemical analyzer was used to detect alanine aminotransferase(ALT),aspartate aminotransferase(AST) activities and urinary creatinine(CRE),urea nitrogen(BUN),blood calcium and blood phosphorus levels in serum;Western blotting were used to detect p63,C-X-C motif chemokine receptor 4(CXCR4) and matrix metalloproteinase 9(MMP9)protein expressions in femoral tissue.Results Compared with model group,combination of Liuwei Dihuang Decoction and Sansheng Powder with zoledronic acid significantly decreased the activities of ALP,AST,ALT and levels of CRE,BUN,calcium and phosphorus in serum of mice(P < 0.05).Expression of p63 in femoral tissue was up-regulated(P < 0.05),and expressions of CXCR4 and MMP9in femoral tissue were significantly down-regulated(P < 0.05).Conclusion Liuwei Dihuang Decoction combined with Sansheng Powder and zoledronic acid can delay the process of bone metastasis of prostate cancer by up-regulating the expression of p63 and inhibiting the expressions of CXCR4 and MMP9.

关 键 词：六味地黄汤 三圣散 唑来膦酸 前列腺癌 骨转移 

分 类 号：R285.5[医药卫生—中药学]