肺岩宁方对Lewis肺癌小鼠肿瘤浸润性髓样细胞的调控作用研究  

Effect of Feiyanning Formula on Tumor-Infiltrating Myeloid Cells of Mice with Lewis Lung Cancer

作　　者：张琦君 殷书敏 车勇 祝利民[2] 罗振东 郭玉刚 徐振晔[2] ZHANG Qijun;YIN Shumin;CHE Yong;ZHU Limin;LUO Zhendong;GUO Yugang;XU Zhenye(Jiangwan Hospital of Hongkou District of Shanghai/The First Affiliated Rehabilitation Hospital of Shanghai University of Medicine&Health Sciences,Shanghai 200434,China;Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine,Shanghai 200032,China)

机构地区：[1]上海市虹口区江湾医院/上海健康医学院附属第一康复医院,上海200434 [2]上海中医药大学附属龙华医院,上海200032

出　　处：《中医药学报》2021年第12期34-40,共7页Acta Chinese Medicine and Pharmacology

基　　金：上海市教育委员会科研创新计划项目(2017-01-07-00-10-E00064);上海市卫生和计划生育委员会中医药科研课题(2018LP006)。

摘　　要：目的:观察肺岩宁方对Lewis肺癌小鼠肿瘤浸润性髓样细胞MDSCs、TAMs的调控作用。方法:选取C57BL/6雄性小鼠建立Lewis肺癌小鼠模型,成模小鼠随机分为模型组、肺岩宁低剂量组、肺岩宁高剂量组,每组8只,另取8只正常小鼠为空白组。空白组、模型组:0.4 mL生理盐水灌胃,每日1次;肺岩宁低剂量组:0.4 mL 40 g/(kg·d)肺岩宁方灌胃,每日1次;肺岩宁高剂量组:0.4 mL 80 g/(kg·d)肺岩宁方灌胃,每日1次。14 d后处死小鼠,剥取肺组织,收集外周血,流式细胞术检测小鼠肺组织MDSCs、M1及M2型TAMs细胞百分比;酶联免疫吸附(ELISA)法检测小鼠外周血IL-4、IL-10表达水平;实时荧光PCR法检测小鼠肺组织中iNOS、Arg-1 mRNA表达水平;免疫印迹法(Western Blot)检测小鼠肺组织PD-1、PD-L1、PI3K、C/EBPβ表达水平。结果:与空白组相比,模型组小鼠肺组织中M1型TAMs百分比显著降低(P<0.05),M2型TAMs、MDSCs百分比显著上升(P<0.05);与模型组相比,肺岩宁低、高剂量组小鼠肺组织中M1型TAMs细胞百分比显著上升(P<0.05),M2型TAMs、MDSCs百分比显著降低(P<0.05)。与空白组相比,模型组、肺岩宁低、高剂量组小鼠血清中IL-4、IL-10水平显著升高(P<0.05);与模型组相比,肺岩宁低、高剂量组小鼠血清中IL-4、IL-10水平显著降低(P<0.05);与肺岩宁低剂量组相比,高剂量组小鼠血清中IL-4、IL-10水平显著降低(P<0.05)。与空白组相比,模型组小鼠肺组织中iNOS mRNA水平显著降低,Arg-1 mRNA水平显著升高(P<0.05);与模型组相比,肺岩宁低、高剂量组小鼠肺组织中iNOS mRNA水平上升,Arg-1 mRNA水平显著降低(P<0.05)。与空白组相比,模型组、肺岩宁低剂量组小鼠肺组织中PD-1、PD-L1、PI3K表达增加(P<0.05),模型组小鼠肺组织中C/EBPβ表达增加(P<0.05);与模型组相比,肺岩宁高剂量组小鼠肺组织中PD-1、PD-L1、PI3K、C/EBPβ表达下调(P<0.05),肺岩宁低剂量组小鼠肺组织中PD-L1表达下调(P<0.05);与�Objective:To observe the regulatory effect of Feiyanning Formula on MDSCs and TAMs of tumor-infiltrating myeloid cells in mice with Lewis lung cancer.Methods:C57 BL/6 male mice were selected to establish Lewis lung cancer model.The successful modeling mice were randomly divided into the model group,the Feiyanning Formula groups of low-dose and high-dose,with 8 mice in each group,and another 8 normal mice were selected as blank control.The blank group and the model group were given 0.4 mL normal saline daily,and the Feiyanning Formula groups of low-dose and high-dose were given 0.4 mL of Feiyanning decoction once a day at the concentration of 40 g/(kg·d)and 80 g/(kg·d)respectively.After 14 days,the samples of lung tissues and blood were collected.The expression levels of MDSCs,M1 and M2 TAMs in lung tissues of mice were detected by flow cytometry,the expression levels of IL-4 and IL-10 in peripheral blood were detected by ELISA,the mRNA expression levels of iNOS and Arg-1 in lung tissues were detected by PCR,and the expression levels of PD-1,PD-L1,PI3K and C/EBPβ in lung tissues were detected by Western blot.Results:Compared to those in the blank group,M1 TAMs percentage in lung tissues was significantly decreased(P<0.05),and the percentages of M2 TAMs and MDSCs were significantly increased in the model group(P<0.05);compared to those in the model group,M1 TAMs percentage in lung tissues was significantly increased(P<0.05),and the percentages of M2 TAM and MDSCs were significantly decreased in the Feiyanning Formula groups of low-dose and high-dose(P<0.05).Compared to those in the blank group,the serum levels of IL-4 and IL-10 were significantly increased in the model group and the Feiyanning Formula groups of low-dose and high-dose(P<0.05);compared to those in the model group,the serum levels of IL-4 and IL-10 were significantly decreased in the Feiyanning Formula groups of low-dose and high-dose(P<0.05);compared to those in the Feiyanning Formula group of low-dose,the serum levels of IL-4 and IL-10 were signi

关 键 词：肿瘤免疫微环境 肿瘤浸润性髓样细胞 髓源性抑制细胞 肿瘤相关性巨噬细胞 肺岩宁方 

分 类 号：R285.5[医药卫生—中药学]