益气养阴方对肺癌小鼠肠道微生态的影响及可能的调控机制分析

Effect and Mechanism of Supplementing Qi and Nourishing Yin Decoction on Intestinal Microbiome of Mice with Lung Carcinoma

目的 研究益气养阴方（SQNY）对肺癌小鼠经顺铂处理后肠道微生态的影响及可能的调控机制。方法 建立C57BL/6小鼠Lewis肺癌模型;分别给予生理盐水（NC组）、顺铂（DDP组）、CAP方案（CAP组）、DDP＋SQNY;观察各组动物肿瘤体积、体重以及肠道粪便菌群比例、血清白细胞介素（IL）-6、IL^-10、肿瘤坏死因子-α（TNF-α）含量;采用流式细胞术法检测各组动物脾脏组织中树突状细胞（DC）和巨噬细胞的含量。结果 自给药3 d后,DDP组、CAP组、DDP＋SQNY组小鼠肿瘤体积明显小于NC组,且DDP＋SQNY组小鼠肿瘤体积和最终瘤重最小（P〈0.05）。NC组和DDP＋SQNY组动物体重变化率基本一致,均高于DDP组和CAP组小鼠（P〈0.05）。经ELISA检测,DDP＋SQNY组小鼠血清IL-6、IL^-10及TNF-α含量明显低于NC组、DDP组和CAP组小鼠（P〈0.05）。DDP＋SQNY组小鼠粪便菌群丰度明显低于其他3组,且在门水平,厚壁菌门比例较其他3组明显升高,拟杆菌门比例明显减低;在属水平,乳酸杆菌比例明显升高（P〈0.05）。DDP＋SQNY组小鼠脾脏内DC数量以及巨噬细胞M1/M2比值明显高于其他3组（P〈0.05）。结论 SQNY可提高DDP治疗后肺癌小鼠抗肿瘤免疫功能,改变肠道菌群的组成,从而降低机体炎症水平,配合化疗药物减毒增效。

OBJECTIVE To discuss the effect and mechanism of supplementing qi and nourishing yin（SQNY） decoction on in- testinal microbiome of mice with Lewis lung carcinoma after treated with cisplatin. METHODS The model of C57BL/6 mice with lung carcinoma xenograft was established by subcutaneous seeding of Lewis cells and randomly divided into 4 groups （n = 16 ） , including saline group （NC group） , cisplatin group （DDP group） , CAP group （CAP group） and SQNY decoction combined with eisplatin group （ DDP ＋ SQNY group）. The tumor sizes, weights and intestinal microbiota were detected. The serum levels of IL-6, IL-10, and TNF-α were detected by ELISA. The dendritic cell （DC） and macrophage subtype in spleen of mice models were detected by flow cytometry. RESULTS ①The mean tumor sizes of mice in DDP group, CAP group, DDP ＋ SQNY groups were all smaller than NC group （ P 〈 0. 05 ）. And the mean tumor size and weight in DDP ＋ SQNY group were less than the other three groups （ P 〈 0. 05 ）. The mean animal weights in NC or DDP ＋ SQNY group were higher than those in DDP group and CAP group （ P 〈 0. 05 ）.②The mean levels of serum IL-6, IL-10 and TNF-α in DDP ＋ SQNY group were less than those in the other three groups （ P 〈 0. 05）. ③The mean microbiota richness in DDP ＋ SQNY group were less than those in the other three groups （ P 〈 0. 05 ）. The proportion of fecal microbiota was significantly changed in DDP ＋ SQNY group, including upregulation of Firmicutes phylum and Bifidobacterium Genus, and downregulation of Bacteroidetes phylum（ P 〈0. 05）. ④The amount of DC and M1/M2 macrophage subtype in spleen of DDP ＋ SQNY group mice models were more than those in the other three groups （P 〈 0. 05）. CONCLUSION It＇s suggested that SQNY decoction effectively enhances the anticancer effect of cisplatin by increasing the immune function and changing the intestinal microbiota.