基于肠道菌群探讨健脾通络方抗大肠癌机制  

Mechanism of Jianpi Tongluo Formula(健脾通络方)in Treatment of Colorectal Cancer Based on Intestinal Flora

作　　者：崔文文 袁秋环[3] 孙景仙[1] 管忠安[1] CUI Wenwen;YUAN Qiuhuan;SUN Jingxian;GUAN Zhongan(Affiliated Hospital of Shandong University of Traditional Chinese Medicine,Jinan 250014,China;Shandong University of Traditional Chinese Medicine,Jinan 250355,China;Qilu Hospital of Shandong University,Jinan 250012,China)

机构地区：[1]山东中医药大学附属医院,山东济南250014 [2]山东中医药大学,山东济南250355 [3]山东大学齐鲁医院,山东济南250012

出　　处：《山东中医药大学学报》2025年第2期204-214,255,共12页Journal of Shandong University of Traditional Chinese Medicine

基　　金：山东省自然科学基金项目(编号:ZR2021MH399);国家中医优势专科建设项目(编号:YWC2023ZYYSY0002);齐鲁中医药优势专科集群建设项目(编号:YWC2022ZKJQ0003);全国名老中医药专家姜春英传承工作室建设项目;山东省中医药科技发展计划项目(编号:2019-0070)。

摘　　要：目的:从肠道菌群角度探讨健脾通络方联合5-氟尿嘧啶(5-FU)对结肠癌CT26荷瘤小鼠的疗效及作用机制。方法:将40只BALB/c小鼠随机分为空白对照组、模型对照组、中药组、5-FU组、联合治疗组,每组8只。除空白对照组外,其余4组构建CT26.WT结肠癌皮下移植瘤模型。造模成功后给予药物治疗,中药组予健脾通络方23.11 g/kg灌胃,每日1次;5-FU组予5-FU25 mg/kg腹腔注射,隔日1次;联合治疗组予健脾通络方和5-FU,用法用量同前;空白对照组及模型对照组每日灌胃23.11 g/kg生理盐水,连续灌胃14 d,同时隔日1次腹腔注射25 mg/kg化疗药溶剂。给药期间隔日测量小鼠肿瘤体积,绘制肿瘤生长曲线。治疗14 d后剥离肿瘤、脾脏,称取瘤重、脾脏质量,计算抑瘤率、脾指数。无菌收集各组小鼠粪便,采用16SrDNA测序技术检测各组小鼠肠道菌群的变化情况。采用酶联免疫吸附(ELISA)试剂盒检测各组小鼠血清中白细胞介素-2(IL-2)含量。结果:与模型对照组相比,各用药组移植瘤的生长均受到了抑制,肿瘤生长曲线减缓,瘤体质量减轻,差异均有统计学意义(P<0.05,P<0.01,P<0.001);与中药组相比,联合治疗组肿瘤体积缩小,瘤体质量减轻,差异均有统计学意义(P<0.05,P<0.01);中药组抑瘤率为24.88%,5-FU组抑瘤率为40.86%,联合治疗组抑瘤率为54.29%。与空白对照组相比,模型对照组脾指数、IL-2含量降低,差异有统计学意义(P<0.05);与模型对照组、5-FU组比较,中药组、联合治疗组脾指数、IL-2显著升高,差异均有统计学意义(P<0.01,P<0.001)。肠道菌群结果显示,种瘤后Firmicutes/Bacteriodota下降;与空白对照组相比,中药组、联合治疗组Chao1指数升高(P<0.05,P<0.001),与5-FU组比较,中药组Chao1指数升高(P<0.01);与空白对照组比较,中药组、联合治疗组Shannon指数有升高趋势,与5-FU比较,中药组Shannon指数有升高趋势,中药组的优势菌主要为g_Alistipes(P<0.05)。结论:Objective:To investigate the therapeutic effect and mechanism of Jianpi Tongluo Formula(健脾通络方)combined with 5-Fluorouracil(5-FU)on colon cancer CT26 tumor-bearing mice from the perspective of intestinal flora.Methods:Total 40 BALB/c mice were randomly divided into blank control group,model control group,traditional Chinese medicine(TCM)group,5-Fluorouracil(5-FU)group and combined treatment group,with 8 mice in each group.Except for the blank control group,the CT26.WT colon cancer subcutaneous transplantation tumor model was constructed in the other 4 groups.After successful modeling,drug treatment was given.The TCM group was given intragastric administration of 23.11 g/kg Jianpi Tongluo Decoction once a day;the 5-FU group was given intraperitoneal injection of 25 mg/kg 5-FU once every other day;the combined treatment group was given Jianpi Tongluo Decoction and 5-FU,with the same usage and dosage as before.The blank control group and the model control group were given 23.11 g/kg normal saline daily for 14 days,and 25 mg/kg chemotherapeutic solvent was injected intraperitoneally once every other day.During the treatment period,the tumor volume of mice was measured every other day and growth curve was plotted.After 14 days of treatment,the tumor and spleen were removed,the tumor weight and spleen weight were measured to calculate tumor inhibition rate and spleen index.Feces of mice in each group were aseptically collected to detect the changes of fecal intestinal flora using 16 rDNA sequencing technique.The serum levels of interleukin-2(IL-2)were detected by using enzyme-linked immunosorbent assay(ELISA)kit.Results:Compared with the model control group,the growth of transplanted tumor was inhibited,the tumor growth curve was slowed down and the tumor weight reduced in each drug group,with statistically significant difference(P<0.05,P<0.01,P<0.001).Compared with the TCM group,the tumor size and tumor weight reduced in the combined treatment group(P<0.05,P<0.01).The tumor inhibition rate was 24.88%in the TC

关 键 词：健脾通络方 大肠癌 肠道菌群 作用机制 

分 类 号：R735.34[医药卫生—肿瘤]