淫羊藿苷调控鼻咽癌免疫逃逸：基于Treg/Th平衡重建与PD-1/PD-L1通路抑制的机制

李祥东; 袁丽芳; 彭先丽

文章摘要

淫羊藿苷调控鼻咽癌免疫逃逸：基于Treg/Th平衡重建与PD-1/PD-L1通路抑制的机制

Regulation of immune escape in nasopharyngeal carcinoma by icariin: mechanisms involving Treg/Th balance restoration and PD-1/PD-L1 pathway inhibition

投稿时间：2025-05-17

DOI：10.3969/j.issn.1000-0399.2026.01.004

中文关键词: 淫羊藿苷鼻咽癌 T细胞亚群程序性死亡受体1/程序性死亡配体1

英文关键词: Icariin Nasopharyngeal carcinoma T cell subsets programmed cell death protein 1/programmed death-ligand 1

基金项目:广东省中医药局科研项目(编号:20221359)

作者	单位
李祥东	519040 广东珠海广东省人民医院珠海医院（珠海市金湾中心医院）耳鼻咽喉科
袁丽芳	519040 广东珠海广东省人民医院珠海医院（珠海市金湾中心医院）健康管理中心
彭先丽	519040 广东珠海广东省人民医院珠海医院（珠海市金湾中心医院）检验科

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中文摘要:

目的探讨淫羊藿苷通过干预调节性T细胞/辅助性T细胞（Treg/Th）平衡及程序性死亡受体1/程序性死亡配体1（PD-1/PD-L1）通路抑制鼻咽癌免疫逃逸的作用机制。方法采用腋部皮下注射二亚硝基哌嗪构建鼻咽癌大鼠模型。选择造模成功的大鼠30只，随机分为模型组（10只）、淫羊藿苷低剂量组（20 mg/kg,10只）和高剂量组（50 mg/kg,10只），另设正常对照组（10只）。通过苏木精-伊红（HE）染色观察各组鼻咽组织病理形态；Western blot检测各组鼻咽组织血管内皮生长因子（VEGF）、基质金属蛋白酶-9（MMP-9）及单核细胞PD-1/PD-L1表达；酶联免疫吸附试验（ELISA）法及流式细胞术分析测定各组大鼠末次给药后外周血白细胞介素-10（IL-10）、转化生长因子-β（TGF-β）水平，CD4⁺T、CD8⁺T百分比及Treg（CD4⁺CD25⁺T）细胞比例。结果与对照组比较，模型组鳞状上皮增生、核异型及炎性浸润，肿瘤微环境表现为促癌因子（VEGF、MMP-9）及免疫抑制指标（Treg、IL-10、TGF-β、PD-1/PD-L1）上调（P<0.05），而效应T细胞（CD4⁺T、CD8⁺T）比例下降（P<0.05）。淫羊藿苷干预后，高、低剂量组均剂量依赖性逆转上述病理特征及免疫失衡（P<0.05），其中高剂量组明显抑制PD-1/PD-L1表达并恢复效应T细胞比例（P<0.05）。结论淫羊藿苷可能通过协同抑制Treg细胞扩增及PD-1/PD-L1信号轴，重塑Th免疫稳态，逆转肿瘤免疫抑制微环境，从而阻断鼻咽癌免疫逃逸进程。

英文摘要:

Objective To investigate the mechanism by which icariin inhibits immune escape in nasopharyngeal carcinoma by modulating the regulatory T cell/helper T cell（Treg/Th） balance and the programmed cell death protein 1/programmed death-ligand 1（PD-1/PD-L1）pathway.Methods A rat NPC model was established by subcutaneous injection of dinitrosopiperazine into the axilla.A total of 30 successfully modeled rats were selected and randomly divided into the model group（n=10）,the low-dose icariin group（20 mg/kg,n=10）,and the high-dose icariin group（50 mg/kg,n=10）.A normal control group（n=10） was also established separately.HE staining was employed to observe the pathological morphology of nasopharyngeal tissue in each group.Western blot was used to detect the expression of vascular endothelial growth factor（VEGF）,matrix metalloproteinase-9（MMP-9）,and PD-1/PD-L1 on monocytes in the nasopharyngeal tissue of each group.ELISA and flow cytometry were employed to analyze the levels of interleukin-10（IL-10） and transforming growth factor-β（TGF-β） in peripheral blood,the percentages of CD4⁺T and CD8⁺T cells,and the proportion of Treg（CD4⁺CD25⁺T） cells after the last administration.Results Compared with the control group,the model group exhibited squamous epithelial hyperplasia,nuclear atypia,and inflammatory infiltration.The tumor microenvironment showed upregulation of pro-carcinogenic factors（VEGF,MMP-9） and immunosuppressive indicators（Treg cells,IL-10,TGF-β,PD-1/PD-L1）(P<0.05),while the proportion of effector T cells（CD4⁺T,CD8⁺T） decreased（P<0.05）.Icariin intervention dose-dependently reversed these pathological features and immune imbalances in both the high-and low-dose groups（P<0.05）.Notably,the high-dose group significantly suppressed PD-1/PD-L1 expression and restored the proportion of effector T cells（P<0.05）.Conclusion Icariin may block the immune escape process in nasopharyngeal carcinoma by synergistically inhibiting Treg cell expansion and the PD-1/PD-L1 signaling axis,thereby reshaping Th immune homeostasis and reversing the tumor immunosuppressive microenvironment.

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