黄芪通过促进滤泡辅助性T细胞活性抑制小鼠肾细胞癌生长  

Astragalus membranaceus inhibits renal cell carcinoma growth by promoting follicular helper T cell activity in mice

作　　者：蔡晨[1] 徐沈倩 杜婷婷[1] 刘玲[1] 蒲瑾[1] 董勤 CAI Chen;XU Shen-qian;DU Ting-ting;LIU Ling;PU Jin;DONG Qin(Department of VIP Medicine,Changhai Hospital,Naval Medical University(Second Military Medical University),Shanghai 200433,China;Department of Nephrology,Hospital of Shanghai Armed Police,Shanghai 201103,China)

机构地区：[1]海军军医大学(第二军医大学)长海医院特需诊疗科,上海200433 [2]武警上海市总队医院肾内科,上海201103

出　　处：《第二军医大学学报》2021年第6期651-656,共6页Academic Journal of Second Military Medical University

基　　金：上海市自然科学基金面上项目(17ZR1438600);上海市长宁区科学技术委员会课题(CNKW2018Y34)。

摘　　要：目的探讨黄芪通过促进滤泡辅助性T细胞(Tfh细胞)活性抑制肾细胞癌生长的作用。方法取56只BALB/c小鼠建立肾细胞癌模型,并随机平均分为黄芪治疗组和对照组。黄芪治疗组小鼠每天通过管饲法予0.5 mg/g黄芪提取物干预,对照组则每天给予相同体积的纯净水。两组建模后第0、9、12、15、18、21天分别处死3只小鼠,通过测量肿瘤的体积评价黄芪提取物对肾细胞癌生长的影响,采用流式细胞术分析肿瘤组织中Tfh细胞的比例。两组建模后第21天处死余10只小鼠,采用流式细胞术检测CD8+T细胞和Tfh细胞比例,通过检测细胞因子表达探讨黄芪提取物对Tfh细胞的作用。结果建模后第18、21天,与对照组相比,黄芪治疗组小鼠的肿瘤体积较小(P<0.05),并伴有肿瘤组织内Tfh细胞浸润增加(P<0.05)。建模后第21天,黄芪治疗组Tfh细胞中IL-21 mRNA表达水平高于对照组Tfh细胞(P<0.05),并且肿瘤中浸润性CD8+T细胞的比例与浸润性Tfh细胞的比例及Tfh细胞中IL-21 mRNA的表达水平均呈正相关(r^(2)=0.700、0.673,P=0.003、0.004)。结论黄芪干预可使小鼠肾细胞癌生长变慢,并且可能通过Tfh细胞发挥抗肿瘤免疫效应。Objective To explore the inhibiting effect of Astragalus membranaceus on the growth of renal cell carcinoma by promoting the activity of follicular helper T cells(Tfh cells).Methods A mouse model of renal cell carcinoma was established in 56 BALB/c mice,and then they were evenly divided into Astragalus membranaceus treatment group and control group.The mice in the Astragalus membranaceus treatment group were given 0.5 mg/g Astragalus membranaceus extract by tube feeding every day,while the mice in the control group were given the same volume of purified water every day.Three mice were sacrificed on days 0,9,12,15,18 and 21 respectively after modeling in both groups,the effect of Astragalus membranaceus extract on the growth of renal cell carcinoma was evaluated by measuring the tumor volume,and the Tfh cell proportion in tumor tissue was analyzed by flow cytometry.The remaining 10 mice were sacrificed on day 21 after modeling in both groups,the proportions of CD8+T cells and Tfh cells were detected by flow cytometry,and the effect of Astragalus membranaceus extract on Tfh cells was explored by detecting the expression of cytokines.Results Compared with the control group,the volume of tumor in the Astragalus membranaceus treatment group was significantly smaller on days 18 and 21(P<0.05),accompanied by an increase in Tfh tumor infiltration(P<0.05).The mRNA expression level of interleukin 21(IL-21)in Tfh cells of the Astragalus membranaceus treatment group was significantly higher than that of the control group on day 21(P<0.05),and the proportion of tumor-infiltrating CD8+T cells was positively correlated with the proportion of tumor-infiltrating Tfh cells(r^(2)=0.700,P=0.003)and the mRNA expression level of IL-21 in Tfh cells(r^(2)=0.673,P=0.004).Conclusion Astragalus membranaceus can slow down the growth of renal cell carcinoma in mice,and may exert anti-tumor immune effects through Tfh cells.

关 键 词：黄芪 滤泡辅助性T细胞 肾细胞癌 白细胞介素21 

分 类 号：R737.11[医药卫生—肿瘤] R286.91[医药卫生—临床医学]