调脾安肠方对伊立替康致迟发性腹泻小鼠肠道菌群的影响  

Effects of decoction for regulating spleen and calming intestine on intestinal flora in irinotecan delayed diarrhea in mice

作　　者：孙小梅 苏菲[2] 刘猛[2] 王佳聪 程志强[2] SUN Xiaomei;SU Fei;LIU Meng;WANG Jiacong;CHENG Zhiqiang(Beijing University of Chinese Medicine,Beijing 100029,China;China-Janan Friendship Hospital,Beijing 100029,China)

机构地区：[1]北京中医药大学,北京100029 [2]中日友好医院,北京100029

出　　处：《现代中西医结合杂志》2024年第9期1169-1180,共12页Modern Journal of Integrated Traditional Chinese and Western Medicine

基　　金：中央高水平医院临床科研业务费资助项目(2022-NHLHCRF-LX-02-0109);中日友好医院科研基金资助项目(2019-1-QN-56)。

摘　　要：目的研究调脾安肠方对伊立替康致迟发性腹泻小鼠肠道菌群结构及其毒性代谢产物活性的影响。方法将32只健康BALB/c雌性小鼠随机分为空白组、模型组、调脾安肠方组、黄连素组,每组8只。除空白组外,其余3组小鼠制备CT26皮下荷瘤模型后再建立伊立替康致迟发性腹泻模型,从伊立替康腹腔注射当天开始,调脾安肠方组每天于化疗前2 h给予调脾安肠方浓缩制剂0.4 mL(28 g/kg)灌胃,模型组每天于化疗前2 h给予生理盐水0.4 mL灌胃,黄连素组每天于化疗前2 h给予盐酸小檗碱片水溶液0.4 mL灌胃(100 mg/kg),空白组与造模组相同时间段给予生理盐水0.4 mL灌胃,均连续灌胃10 d。于实验结束后当天留取各组小鼠粪便,分光光度法检测粪便样本中β-葡萄糖醛酸苷酶活性,16S rRNA高通量测序技术检测样本中肠道菌群结构及分布情况。结果模型组β-葡萄糖醛酸苷酶活性明显高于空白组(P<0.05);调脾安肠方组及黄连素组β-葡萄糖醛酸苷酶活性均明显低于模型组(P均<0.05),且调脾安肠方组明显低于黄连素组(P<0.05)。粪便样本测序显示,模型组小鼠肠道菌群物种丰度、均匀度及多样性下降,而调脾安肠方组小鼠肠道菌群物种丰度、均匀度及多样性均得到逆转,趋近于正常小鼠,且在菌群物种组成上与空白组相似,黄连素组与模型组相似;空白组及调脾安肠方组OTUs数量较多,其次为黄连素组,模型组数量最少;肠道菌群物种门水平分析,各组样本中厚壁菌门(Firmicutes)和拟杆菌门(Bacteroidetes)丰度均较高,其中疣微菌门(Verrucomicrobia)、变形菌门(Proteobacteria)在模型组样本中具有较高丰度;肠道菌群物种属水平分析,乳杆菌属(Lactobacillus)在各组均有较高丰度,模型组样本中阿克曼菌属(Akkermansia)、拟杆菌属(Bacteroides)丰度降低,调脾安肠方组丰度上调至接近正常水平;各组OTUs相比,模型组小鼠肠道菌群中丹毒丝菌目�Objective It is to study the effects of decoction for regulating spleen and calming intestine on the structure of intestinal flora and its toxic metabolite activity in mice with irinotecan delayed diarrhea.Methods Thirty-two healthy BALB/c female mice were randomly divided into 4 groups:blank group,model group,decoction for regulating spleen and calming intestine group,berberine group,with 8 mice in each group.The models of irinotecan delayed diarrhea were established after CT26 subcutaneous tumor-bearing models were prepared in the mice of all groups except for the blank group.Starting from the day of the intraperitoneal injection of irinotecan,the decoction for regulating spleen and calming intestine group was given concentrating preparation of decoction for regulating spleen and calming intestine 0.4 mL(28 g/kg)by gavage 2 h before chemotherapy every day,the model group was given normal saline 0.4 mL by gavage 2 h before chemotherapy every day,the berberine group was given berberine hydrochloride tablet solution 0.4 mL(100 mg/kg)by gavage 2 h before chemotherapy every day,the blank group was given normal saline 0.4 mL by gavage at the same time period,all continuously treated for 10 days.The feces of mice in each group were collected on the day of the end of the experiment,theβ-glucuronidase activity in the fecal samples was detected by spectrophotometry,and the structure and distribution of the intestinal flora in the samples were detected by 16S rRNA high-throughput sequencing technology.Results Theβ-glucuronidase activity of the model group was significantly higher than that of the blank group(P<0.05);theβ-glucuronidase activities of both the decoction for regulating spleen and calming intestine group and berberine group were significantly lower than that of the model group(both P<0.05),and the decoction for regulating spleen and calming intestine group was significantly lower than the berberine group(P<0.05).Sequencing of fecal samples showed that the abundance,homogeneity and diversity of intestinal fl

关 键 词：调脾安肠方 伊立替康 迟发性腹泻 肠道菌群 Β-葡萄糖醛酸苷酶 

分 类 号：R-332[医药卫生]