黄连解毒汤联合程序性死亡受体1抗体通过重塑免疫微环境对乳腺癌的作用研究  

Study on the Mechanism of Huanglian Jiedu Decoctions Combined withαPD-1 to Reshape Immune Microenvironment in the Treatment of Breast Cancer

作　　者：周晓雯 张天南 ZHOU Xiaowen;ZHANG Tiannan(Department of Pharmacy,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药学部,南京210029

出　　处：《药学与临床研究》2024年第5期391-396,共6页Pharmaceutical and Clinical Research

基　　金：国家自然科学基金资助项目(82003834);江苏省中医药管理局科技项目(YB2020013)。

摘　　要：目的:探讨黄连解毒汤(HLJD)联合程序性死亡受体1抗体(αPD-1)对乳腺癌小鼠肿瘤的影响。方法:建立原位Balb/C乳腺癌小鼠模型,将其分为模型组、HLJD组、αPD-1组和联合给药组。通过小鼠肿瘤体积的变化、肿瘤组织的苏木素-伊红(H&E)染色评估联合治疗的抗肿瘤效果;利用免疫荧光法检测肿瘤组织中CD_(8)^(+)T细胞的浸润;ELISA法检测小鼠血清中白介素-2(IL-2)、转化生长因子-β(TGF-β)和干扰素γ(IFN-γ)细胞因子分泌水平;流式细胞术分析小鼠肿瘤和脾脏中CD_(8)^(+)T细胞、细胞毒性T细胞(CTL细胞)、Treg细胞的比例以及引流淋巴结中抗原递呈细胞DC细胞的活化。结果:黄连解毒汤联合αPD-1可以明显缩小肿瘤体积,增加肿瘤组织中CD_(8)^(+)T细胞的浸润,上调肿瘤组织和脾脏中CTL的比例,同时下调Treg比例,促进引流淋巴结中DC细胞活化,促进血清中IL-2和IFN-γ细胞因子的分泌。结论:黄连解毒汤可通过调节免疫微环境增强αPD-1对乳腺癌的抑制效果。Objective:To investigate the effects of HLJD combined withαPD-1 on breast cancer in mice.Methods:In situ Balb/C breast cancer mouse model was established and the mice were divided into model group,HLJD group,αPD-1 group and combination group.Anti-tumor effects were evaluated through tumor volume,survival time and hematoxylin eosin(H&E)staining of tumor tissue in mice.Immunofluorescence was used to detect the infiltration of CD_(8)^(+)T cells in tumor tissue.An ELISA method was applied for detecting cytokine secretion levels IL-2,IFN-γand TGF-βin mouse serum.Flow cytometry was used to analyze the proportion of CTL and Treg cells in mouse tumors and spleens,as well as the activation of antigen-presenting DC cells in draining lymph nodes.Results:HLJD combined withαPD-1 significantly reduced tumor volume,increased CD_(8)^(+)T cell infiltration in tumors,up-regulated CTL ratio and down-regulated Treg ratio in the tumors and spleens,promoted DC activation in draining lymph nodes,and promoted IL-2 and IFN-γsecretion in serum.Conclusion:HLJD may promote the inhibitory effects ofαPD-1 on breast cancer by regulating the immune microenvironment.

关 键 词：αPD-1 黄连解毒汤 乳腺癌 免疫微环境 细胞毒性T细胞 调节性T细胞 

分 类 号：R285.5[医药卫生—中药学]