逍遥散降低情志应激诱导的乳腺癌“易感性”的作用机制研究  

Xiaoyaosan Alleviates Breast Cancer Susceptibility in Emotional Stress Mice

作　　者：吴燕萍[1,2,3] 罗祥 周青青 龚海标 梁磊 李怡芳 栗原博[1,4] 陈家旭[2] 何蓉蓉 WU Yanping;LUO Xiang;ZHOU Qingqing;GONG Haibiao;LIANG Lei;LI Yifang;KURIHARA Hiroshi;CHEN Jiaxu;HE Rongrong(Guangdong Engineering Research Center of Chinese Medicine&Disease Susceptibility,Jinan University,Guangzhou 510632,China;School of Traditional Chinese Medicine,Jinan University,Guangzhou 510632,China;Integrated Chinese and Western Medicine Postdoctoral Research Station,Jinan University,Guangzhou 510632,China;College of Pharmacy,Jinan University,Guangzhou 510632,China)

机构地区：[1]广东省疾病易感性及中医药研发工程技术研究中心/暨南大学,广州510632 [2]暨南大学中医学院,广州510632 [3]暨南大学中西医结合博士后流动站,广州510632 [4]暨南大学药学院,广州510632

出　　处：《世界中医药》2023年第7期973-978,共6页World Chinese Medicine

基　　金：国家自然科学基金项目(82004231,81973718,81630104);中国博士后科学基金资助项目(2020M683204);广东省基础与应用基础研究基金项目(2020A1515110388)。

摘　　要：目的:从巨噬细胞吞噬功能角度探讨逍遥散缓解情志应激诱导的乳腺癌“易感性”的作用机制。方法:将20只小鼠采用完全随机方法分为对照组、模型组、低剂量逍遥散组、高剂量逍遥散组,每组5只。小鼠连续28 d给予拘束应激或低、高剂量的逍遥散(3.25 g/kg,6.50 g/kg),在第7天皮下接种4T1小鼠乳腺癌细胞建立小鼠荷瘤模型,记录小鼠的瘤径、瘤重以及肿瘤拍照。小鼠取材后通过高效液相-紫外分光法检测血浆中皮质酮的含量;免疫组织化学方法观察肿瘤组织中巨噬细胞吞噬现象;采用蛋白质印迹法、实时荧光定量反转录聚合酶链反应(RT-qPCR)、免疫荧光技术检测肿瘤组织中“吃我”信号受体低密度脂蛋白受体相关蛋白(LRP1)、“不吃我”信号受体信号调节蛋白α(SIRPα)和微RNA(miRNA)的表达情况。结果:与模型组比较,低、高剂量逍遥散组显著缓解应激诱导的乳腺癌“易感性”,抑制肿瘤组织中巨噬细胞的吞噬功能,其作用与促进巨噬细胞LRP1的蛋白和基因表达水平,抑制SIRPα蛋白表达有关(P<0.05);逍遥散对巨噬细胞的调节作用,与增加miRNA-4259/6680-5p/7847-3p表达有关(P<0.05)。结论:逍遥散降低情志应激诱导的乳腺癌“易感性”,其作用机制与缓解LRP1-SIRPα信号紊乱并促进巨噬细胞对肿瘤细胞的吞噬作用有关。Objective:To investigate the mechanism of Xiaoyaosan(XYS)in alleviating breast cancer susceptibility in emotional stress mice from the perspective of macrophage phagocytosis.Methods:Twenty mice were randomly assigned into four groups:control,model,model+low-dose XYS,and model+high-dose XYS(n=5).Mice received 28 days of restraint stress for 2 h or/and XYS(3.25,6.50 g/kg)treatment daily and were subcutaneously injected with 4T1 breast cancer cells on the 7th day of stress.The tumor was photographed,and the tumor diameter and tumor weight were measured.The corticosterone(CORT)content in plasma was determined by the high performance liquid chromatography-ultraviolet(HPLC-UV)method.Immunohistochemical staining was employed to determine the phagocytosis of tumor cells by macrophages.Western blotting,RT-qPCR,and immunofluorescence staining were performed to examine the expression of low-density lipoprotein receptor-related protein 1(LRP1),signal-regulatory proteinα(SIRPα),and miRNAs in the tumor tissue.Results:Compared with the model group,XYS relieved emotional stress-evoked breast cancer susceptibility,the mechanism of which was associated with inhibiting the phagocytosis of tumor cells by macrophages through evoking LRP1 expression and down-regulating SIRPαexpression(P<0.05).Further,XYS regulated the phagocytosis by up-regulating the expression of miRNA-4259/6680-5p/7847-3p(P<0.05).Conclusion:XYS ameliorates emotional stress-induced breast cancer susceptibility by preventing the disturbance of LRP1-SIRPαsignals and promoting the phagocytosis of tumor cells by macrophages.

关 键 词：情志应激 乳腺癌 逍遥散 巨噬细胞 低密度脂蛋白受体相关蛋白 信号调节蛋白α 吞噬作用 微RMA 

分 类 号：R285.5[医药卫生—中药学]