柴胡-浙贝药对及其单体成分干预乳腺癌癌前病变的机制研究  

Investigating the mechanism of Chaihu-Zhebei medicinal couplet(柴胡-浙贝药对)and its monomer components in intervening breast cancer precancerous lesions

作　　者：张文可 程旭锋[1] 徐留燕 赵慧朵[1] 刘琦[3] ZHANG Wen-ke;CHENG Xu-feng;XU Liu-yan;ZHAO Hui-duo;LIU Qi(First Affiliated Hospital of Henan University of Chinese Medicine,Zhengzhou 450046,China;Affiliated Longhua Hospital of Shanghai University of Traditional Chinese Medicine,Shanghai 200000,China;Henan University of Chinese Medicine,Zhengzhou 450046,China)

机构地区：[1]河南中医药大学第一附属医院,河南郑州450046 [2]上海中医药大学附属龙华医院,上海200000 [3]河南中医药大学,河南郑州450046

出　　处：《时珍国医国药》2025年第6期1050-1055,共6页Lishizhen Medicine and Materia Medica Research

基　　金：河南省科技攻关计划(222102310326);河南省中医药科学研究专项(2022ZY1048);国家中医优势专科建设项目[国中医药医政函(2024)90号]。

摘　　要：目的探讨柴胡-浙贝药对及其单体成分对乳腺癌癌前病变大鼠的干预效果及机制。方法将30只SD雌性大鼠随机分为空白组、模型组、他莫昔芬组、柴胡皂苷D-贝母甲素组和柴胡-浙贝组各6只,模型组和药物干预组均采用DMBA联合雌孕激素序贯建立大鼠乳腺癌癌前病变模型。各组均给予相应的干预措施。记录造模前、造模后和给药后各组大鼠的体质量。ELISA法检测血清肿瘤坏死因子-α(TNF-α)、白介素-1β(IL-1β)和白介素-6(IL-6)含量;HE染色观察乳腺组织病理情况;免疫组织化学(IHC)法检测CD31-MVD;RT-PCR法检测血管内皮生长因子(VEGF)、缺氧诱导因子-1α(HIF-1α)表达;Western Blot法检测HIF-1α、Endostatin蛋白表达。结果与空白组比较,模型组大鼠乳腺组织内导管病变严重,表现为重度增生。与模型组相比,药物干预组体质量均上升,乳腺组织内导管形态均得到不同程度的改善,表现为轻度增生,血清TNF-α、IL-1β、IL-6,CD31-MVD,VEGF、HIF-1α的mRNA,HIF-1α蛋白水平显著下降,Endostatin蛋白表达水平显著升高(P<0.05)。结论“柴胡-浙贝”药对及其单体成分可减轻乳腺癌癌前病变大鼠的炎症反应,抑制乳腺组织新生血管的生成,其机制可能与调控VEGF/HIF-1α通路有关。Objective To investigate the intervening effect and mechanism of Chaihu(Bupleuri Radix)-Zhebei(Bulbus Fritillariae Thunbergii)medicinal couplet(柴胡-浙贝药对,CZMC)and its monomeric components on rats with breast cancer precancerous lesions.Methods Thirty female SD rats were randomly divided into the blank group,model group,tamoxifen group,Saikosaponin D-Peimine group and CZMC group,with 6 rats in each group.The rat model of breast cancer precancerous lesions was established by DMBA combined with sequential estrogen-progesterone in the model group and drug intervention groups.Corresponding interventions were administered to each group.Body weight was recorded before and after modeling,and after administration.The contents of serum TNF-α,IL-1βand IL-6 were detected by ELISA.HE staining was used to observe the pathological changes of the mammary tissues.CD31-MVD was detected by IHC.The expressions of VEGF and HIF-1αwere detected by RT-PCR,while the protein expressions of HIF-1αand Endostatin were assessed by Western blot(WB).Results Compared with the blank group,the model group exhibited severe ductal lesions in the mammary tissues,showing severe hyperplasia.Compared with the model group,all drug intervention groups showed increased body weight,improved ductal morphology in the mammary tissues with the manifestation of mild hyperplasia,and significant reductions in serum TNF-α,IL-1β,IL-6,CD31-MVD,VEGF and HIF-1αmRNA levels,and HIF-1αprotein expression.Endostatin protein expression was significantly elevated(P<0.05).Conclusion CZMC and its monomer components can alleviate the inflammatory response in rats with breast cancer precancerous lesions and inhibit the formation of neovascularization in the mammary tissues.The mechanism may be associated with the modulation of VEGF/HIF-1α.

关 键 词：“柴胡-浙贝”药对 柴胡皂苷D-贝母素甲 血管新生 乳腺癌 癌前病变 

分 类 号：R285.5[医药卫生—中药学]