丹鹿胶囊调控PI3K-AKT通路改善乳腺癌前病变的慢性氧化应激机制  

Mechanism of chronic oxidative stress on Danlu Capsules regulating PI3K-AKT pathway to improve breast cancer precancerous lessions

作　　者：王聪[1] 许岩磊[1] 姚昶[1] WANG Cong;XU Yanlei;YAO Chang(Affiliated Hospital of Nanjing University of Chinese Medicine,Nanjing 210029,China)

机构地区：[1]南京中医药大学附属医院,南京210029

出　　处：《中华中医药杂志》2024年第11期6049-6053,共5页China Journal of Traditional Chinese Medicine and Pharmacy

基　　金：江苏省中医院培育项目(No.Y20031);江苏省中医院高峰学术人才培养项目(No.y2018rc11);国家自然科学基金项目(No.81804103)。

摘　　要：目的:探讨丹鹿胶囊调控磷酸肌醇3激酶(PI3K)-蛋白激酶B(AKT)通路改善乳腺癌前病变慢性氧化应激机制。方法:将32只大鼠随机分为空白对照组、模型组、西药组和中药组,每组各8只。除空白对照组外,其余各组均用二甲基苯蒽(DMBA)联合雌孕激素序贯建立乳腺癌前病变模型。造模成功后,空白对照组及模型组大鼠给予0.9%氯化钠注射液10 mL/kg灌胃;西药组大鼠给予枸橼酸他莫昔芬水溶液8 mg/kg灌胃,中药组大鼠给予丹鹿胶囊溶液3 g/kg灌胃,连续灌胃4周。HE染色观察乳腺组织病理变化,ELISA法检测血清孕酮(P)、雌二醇(E2),PI3K、AKT蛋白,比色法测定谷胱甘肽过氧化物酶(GSH-Px)表达水平。结果:模型组、西药组、中药组肿瘤发生率显著高于空白对照组(P<0.05),中药组肿瘤发生率显著低于模型组(P<0.05)。西药组和中药组E2、P水平均显著低于模型组(P<0.05)。西药组和中药组PI3K、AKT蛋白表达水平均显著低于模型组(P<0.05)。西药组和中药组GSH-Px水平均显著高于模型组(P<0.05)。结论:丹鹿胶囊可能是通过降低E2、P的激素分泌,抑制PI3K、AKT蛋白的表达,提高GSH-Px酶活力水平,从而提高体内抗氧化应激水平,实现控制大鼠乳腺癌癌前病变的作用。Objective:To explore the mechanism of Danlu Capsules regulating PI3K-AKT pathway to improve chronic oxidative stress in breast cancer precancerous lesions.Methods:Thirty-two rats were randomly divided into blank group,model group,western medicine group and Chinese medicine group,with 8 rats in each group.In addition to the blank group,the female models of breast cancer precancerous lesions were established by sequential administration of dimethylphenylanthracene(DMBA)combined with estrogen and progesterone in all other groups.After successful modeling,rats in the blank group and model group were given 0.9%sodium chloride injection of 10 mL/kg by gavage;Western medicine group rats were given 8 mg/kg of tamoxifen citrate aqueous solution by gavage,while Chinese medicine group rats were given 3 g/kg of Danlu Capsules solution by gavage for 4 weeks.The pathological changes of breast tissue were observed by HE staining,and the expression levels of serum progesterone(P),estradiol(E2),PI3K protein(phosphoinositol 3 kinase),AKT protein(protein kinase B)and GSH-Px(glutathione peroxidase)were detected by ELISA.Results:The incidence of tumor in the model group,western medicine group and Chinese medicine group was higher than that in the blank group(P<0.05).The incidence of tumor in the Chinese medicine group was lower than that in the model group(P<0.05).E2 and P levels in the western medicine group and the Chinese medicine group were lower than those in the model group(P<0.05).The expression levels of PI3K and AKT protein in western medicine group and Chinese medicine group were lower than those in model group(P<0.05).The level of GSH-Px in the western medicine group and the Chinese medicine group was higher than that in the model group(P<0.05).Conclusion:Danlu Capsules may reduce the hormone secretion of E2 and P,inhibit the expression of PI3K and Akt proteins,and increase GSH-Px.The enzyme activity level increases the level of oxidative stress in vivo,thus realizing the role of controlling precancerous lesions of breast

关 键 词：丹鹿胶囊 乳腺癌前病变 雌激素 枸橼酸他莫昔芬 

分 类 号：R285.5[医药卫生—中药学]