环球中医药2026，Vol.19Issue(5)：982-990,9.DOI:10.3969/j.issn.1674-1749.2026.05.009
基于程序性死亡受体1/程序性死亡配体1信号通路的益气解毒方对肝癌裸鼠恒定自然杀伤T细胞功能的影响
Effect of Yiqi Jiedu Formula on the expression of PD-1 and PD-L1 in iNKT cells and tumor tissues of hepatocellular carcinoma nude mice
摘要
Abstract
Objective To explore the effects of Yiqi Jiedu Formula,a traditional Chinese medicine formula based on the PD-1/PD-L1 signaling pathway,on the function of iNKT cells in hepatocellular carcinome nude mice,and to investigate the mechanism of its anti-tumor effects.Methods Fifty mice,half male and half female,were selected and randomly divided into 10 normal mice and 40 liver cancer model mice.A subcutaneous liver cancer xenograft model in mice was established using Hep3B cells.After successful modeling,the mice were randomly assigned into five groups:traditional Chinese medicine(TCM)groups(low,medium and high doses of the Yiqi Jiedu Formula),model group and Huachansu Tablet group,with 8 mice in each group.The normal and model groups were orally administered 0.2 g/kg normal saline daily;the Huachansu Tablet group received 0.22 g/kg per day,with each tablet containing 250 mg;the high,medium,and low dose TCM groups received daily doses of 0.4 g/kg,0.2 g/kg,and 0.1 g/kg,respectively,for 28 consecutive days.Mice were monitored daily for growth,and tumor weight and volume were recorded to calculate tumor growth inhibition rates.After euthanasia under anesthesia,HE staining was used to observe pathological changes in tumor tissues across groups;flow cytometry was used to evaluate iNKT cell activity;ELISA was employed to detect serum levels of IL-2,IL-4,IL-10,and IFN-γ;Western blot,qRT-PCR,and single immunofluorescence staining were used to detect PD-1 and PD-L1 expression in tumor tissues.Results Compared with the model group,tumor weight and volume were significantly reduced in the TCM and Huachansu Tablet groups(P<0.01,P<0.05)in a dose-dependent manner.Tumor morphology and inflammatory infiltration were improved to varying degrees in the TCM and Huachansu Tablet groups;CD3+,IL-4,and IL-10 levels were significantly decreased in these groups(P<0.01,P<0.05);IL-2,IFN-γ,CD69+/CD 1d+levels were significantly increased compared with the model group(P<0.01,P<0.05);PD-1 and PD-L1 protein and mRNA expression were significantly reduced in the high-dose TCM group and Huachansu Tablet group(P<0.05,P<0.01),while the low-and medium-dose TCM groups showed no significant changes.Tumor growth in the TCM and Huachansu Tablet groups was slower,with smaller volumes and significant tumor inhibition rates compared with the model group.Conclusion The traditional Chinese medicine Yiqi Jiedu Formula can inhibit PD-1/PD-L1 signaling,enhance iNKT cell activity and antitumor immune response,improve the immune microenvironment in hepatocellular carcinoma nude mice and suppress tumor growth.关键词
益气解毒方/肝癌裸鼠/恒定自然杀伤T细胞/程序性死亡受体1/程序性死亡配体1信号通路/作用机制Key words
Yiqi Jiedu Formula/hepatocellular carcinoma nude mice/iNKT cells/PD-1/PD-L1 signaling pathway/mechanism of action分类
医药卫生引用本文复制引用
王震元,张国梁,刘丽丽,韩雅,董丽丽,侯勇,施美..基于程序性死亡受体1/程序性死亡配体1信号通路的益气解毒方对肝癌裸鼠恒定自然杀伤T细胞功能的影响[J].环球中医药,2026,19(5):982-990,9.基金项目
国家自然科学基金(81874451) （81874451）
国家中医药管理局全国名老中医药专家传承工作室建设项目(国中医药人教函[2022]175号) （国中医药人教函[2022]175号）
全国名中医肝胆系疾病学术思想传承及特色方药的临床开发研究(202204295107020040) （202204295107020040）
国家中医药管理局徐经世国医大师传承工作室建设项目(2015072) （2015072）
徐经世国医大师工作室创新团队项目(皖秘2023-11) （皖秘2023-11）
