扶正散结方调节Treg细胞功能抑制肺癌微环境免疫逃逸  

Fuzheng Sanjie Formula Inhibits Immune Evasion in Lung Cancer Microenvironment via Regulating Treg Cell Function

作　　者：张熳媛 潘旭鸣 于双江 宋珈 ZHANG Man-yuan;PAN Xu-ming;YU Shuang-jiang;SONG Jia(Department of Emergency Medicine,the Second Affiliated Hospital of Zhejiang Chinese Medical University,Hangzhou,310005;Department of General Practice,the Second Affiliated Hospital of Zhejiang Chinese Medical University,Hangzhou,310005)

机构地区：[1]浙江中医药大学附属第二医院急诊医学科,杭州310005 [2]浙江中医药大学附属第二医院全科医学科,杭州310005

出　　处：《中国中西医结合杂志》2025年第1期64-69,共6页Chinese Journal of Integrated Traditional and Western Medicine

基　　金：浙江省中医药科技计划项目(No.2023ZR099)。

摘　　要：目的研究扶正散结方干预Treg细胞功能诱导肺癌微环境免疫逃逸的分子机制。方法建立Lewis肺癌小鼠模型,将小鼠随机分为荷瘤模型组、低剂量扶正散结方组(生药0.5 g/mL)、高剂量扶正散结方组(生药2 g/mL)、顺铂组,每组6只,灌胃或腹腔注射给药。接种21天后处死,测量各组小鼠移植瘤体积,称瘤重并计算抑瘤率。HE染色法观察肿瘤组织形态,流式细胞仪检测小鼠血液CD4^(+)CD25^(+)Foxp3^(+)Treg的比例,ELISA法测定小鼠血清IL-10和TGF-β含量,Western Blot检测移植瘤组织程序性死亡分子-1(PD-1)及其配体(PD-L1)表达量。结果模型组肿瘤细胞形态完好,扶正散结方组和顺铂组细胞出现皱缩及坏死等现象。与模型组比较,低、高剂量扶正散结方组和顺铂组小鼠肿瘤体积增长减慢(P<0.001,P<0.05),肿瘤重量增长减慢(P<0.001,P<0.01),抑瘤率增加(P<0.001,P<0.05)。扶正散结方组和顺铂组小鼠血液CD4^(+)CD25^(+)Foxp3^(+)Treg在CD4^(+)T细胞中的比例均降低(P<0.05),小鼠血清IL-10和TGF-β含量降低(P<0.05),PD-1和PD-L1蛋白表达量降低(P<0.05)。结论扶正散结方可通过PD-1/PD-L1信号通路干预Treg细胞功能,抑制肺癌微环境免疫逃逸,进而抑制肿瘤发展。Objective To investigate the molecular mechanisms by which Fuzheng Sanjie Formula modulates Treg cell function to inhibit immune evasion in the lung cancer microenvironment.Methods A Lewis lung cancer mouse model was established.The mice were randomly divided into the tumor model group,the low-dose Fuzheng Sanjie Formula group(0.5 g/mL),the high-dose Fuzheng Sanjie Formula group(2 g/mL),and the cisplatin group,with 6 mice in each group.Drug administration was performed via oral gavage or intraperitoneal injection.After 21 days of inoculation,the mice were sacrificed,and the tumor volume,tumor weight,and tumor inhibition rate were measured.HE staining was used to observe the tumor morphology,flow cytometry was used to analyze the proportion of CD4^(+)CD25^(+)Foxp3^(+)Treg cells in the mouse blood,ELISA was used to measure the levels of IL-10 and TGF-βin the mouse serum,Western Blot was used to detect programmed death 1(PD-1)and programmed death-ligand 1(PD-L1)expression levels in the transplanted tumor tissues.Results The tumor cells in the model group remained intact,while those in the Fuzheng Sanjie Formula groups and cisplatin group exhibited shrinkage and necrosis.Compared with the tumor model group,the tumor volume increase in the low-dose,high-dose Fuzheng Sanjie Formula groups and the cisplatin group was slower(P<0.001,P<0.05),as was the increase in tumor weight(P<0.001,P<0.01),and the tumor inhibition rate increased(P<0.001,P<0.05),the proportions of CD4^(+)CD25^(+)Foxp3^(+)Treg cells in the CD4^(+)T cells decreased(P<0.05),the levels of serum IL-10 and TGF-βwere reduced(P<0.05),as well as PD-1 and PD-L1 protein expressions decreased(P<0.05).Conclusion Fuzheng Sanjie Formula can intervene in Treg cell function through the PD-1/PD-L1 signaling pathway,inhibit immune evasion in the lung cancer microenvironment,and thereby inhibit tumor development.

关 键 词：扶正散结方 细胞调节性T细胞 肺癌微环境 免疫逃逸 中药复方 中西医结合 

分 类 号：R285.5[医药卫生—中药学]