摘要
目的观察益气解毒方对HepG2(人肝癌细胞株)小鼠模型免疫作用的影响,探究益气解毒方在肝癌发展进程中的作用。方法选取小鼠30只,雌雄各半,随机分为空白组5只和造模组25只。造模组小鼠腋下注射HepG2细胞建立异位肝癌小鼠模型,造模成功的小鼠将其随机分为模型组、益气解毒方低、中、高剂量组,每组5只。益气解毒方各剂量组小鼠分别连续4周进行0.2 mL生药浓度为0.5、1、2 g/mL的益气解毒方药液灌胃,模型组和空白组小鼠每天进行0.2 mL生理盐水灌胃,给药过程中记录各组小鼠的肿瘤体积。给药结束后计算抑瘤率,通过流式细胞仪检测HepG2小鼠体内调节性T淋巴细胞(regulatory T cells,Tregs)的表达水平,蛋白免疫印迹法检测叉头样转录因子3(forkhead box p3,Foxp3)及可诱导T细胞共刺激分子蛋白(inducible T-cell co-stimulator,ICOS)的表达,酶联免疫吸附试验检测转化生长因子-β(transforming growth factorβ,TGF-β)、γ-干扰素(interferonγ,IFN-γ)的表达变化。结果益气解毒方各给药组小鼠肿瘤的生长速度较慢,肿瘤体积与模型组相比较小,益气解毒方中、高剂量组的抑瘤效果最为显著;益气解毒方中、高剂量组Treg、Foxp3的表达水平与模型组相比明显降低(P<0.01),益气解毒方各给药组中TGF-β、ICOS的表达水平与模型组相比明显降低(P<0.01),IFN-γ的表达水平显著升高(P<0.01);各组结果对药物呈现剂量依赖性。结论益气解毒方可以抑制肿瘤的生长发展,增强小鼠机体的免疫能力,降低肿瘤免疫逃逸的发生,延缓癌症的进展,其作用机制可能与干预Treg、TGF-β、IFN-γ、Foxp3、ICOS的表达水平有关。
Objective To assess the immunomodulatory effects of Yiqi Jiedu Formula in a mouse model of HepG2(human hepatocellular carcinoma)and elucidate its role in the progression of liver cancer.Methods Thirty mice were randomly assigned to a blank control group(n=5)and a model group(n=25).The model group received subcutaneous injections of HepG2 cells to establish an ectopic liver cancer model.Upon successful tumor induction,mice were randomly divided into four groups:model control,and low-,medium-,and high-dose Yiqi Jiedu treatment groups(n=5 per group).Mice in the treatment groups received intragastric Yiqi Jiedu Formula for four weeks at doses of 0.2 mL with herbal concentrations of 0.5,1,and 2 g/mL,respectively.Control groups received 0.2 mL saline daily.Tumor volumes were measured regularly,and tumor inhibition rates were calculated at the end of the treatment period.Regulatory T cell(Treg)expression levels were analyzed by flow cytometry,while transforming growth factor-β(TGF-β)and interferon-γ(IFN-γ)were quantified using ELISA.Western blotting was employed to assess the expression of forkhead box P3(Foxp3)and inducible T-cell co-stimulator(ICOS)proteins.Results Yiqi Jiedu treatment significantly slowed tumor growth,with smaller tumor volumes observed across treatment groups compared to the model group.Tumor inhibition was most pronounced in the medium-and high-dose groups.Treg and Foxp3 expression levels were markedly lower in the medium-and high-dose Yiqi Jiedu groups compared to the model group(P<0.01).Additionally,TGF-βand ICOS levels were significantly reduced(P<0.01),while IFN-γlevels were significantly elevated(P<0.01)in the Yiqi Jiedu treated groups.These effects were dose-dependent.Conclusion Yiqi Jiedu Formula exhibits potent anti-tumor activity by enhancing immune responses in the mouse model,potentially reducing tumor immune evasion and delaying cancer progression.The underlying mechanisms may be associated with modulation of the Treg/TGF-β/IFN-γ/Foxp3/ICOS.
作者
韩雅
施美
董莉莉
刘丽丽
张国梁
HAN Ya;SHI Mei;DONG Lili;LIU Lili;ZHANG Guoliang(Graduate School of Anhui University of Chinese Medicine,Hefei 230012,China)
出处
《环球中医药》
2025年第1期20-26,共7页
Global Traditional Chinese Medicine
基金
国家自然科学基金(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)
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)。
作者简介
韩雅(1998-),2022级在读硕士研究生。研究方向:中医药防治传染病研究。E-mail:1942599182@qq.com;通信作者:张国梁(1961-),本科,主任医师,教授,硕士生导师。研究方向:中医药防治传染病研究。E-mail:zhangguoliang61@sina.com;施美(博士研究生);刘丽丽(博士研究生)。