| 引用本文:吴燕萍1，2，3，罗祥1，4，周青青1，4，龚海标1，4，梁磊1，4，李怡芳1，4，栗原博1，4，陈家旭2，何蓉蓉1，2，4.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[J].世界中医药,2023,(07):. |
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| 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 |
| 投稿时间：2021-02-05 |
| DOI：10.3969/j.issn.1673-7202.2023.07.013 |
| 中文关键词: 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 |
| English Keywords:Emotional stress Breast cancer Xiaoyaosan Macrophage LRP1 SIRPα Phagocytosis MicroRNA |
| 基金项目: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） |
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| 中文摘要: |
| 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。 |
| English Summary: |
| 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 protein α(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 SIRPα expression(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-SIRPα signals and promoting the phagocytosis of tumor cells by macrophages. |
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