目的 研究甘草泻心汤对化疗相关腹泻小鼠肠道菌群的影响。方法 将小鼠随机分为对照组、模型组、洛哌丁胺（阳性药，0.4 mg·kg^-1）组和甘草泻心汤高、低剂量（16.4、4.1 g·kg^-1）组；采用连续4 d ip 55 mg·kg^-1伊立替康诱导小鼠化疗相关腹泻模型；记录小鼠首次排便时间、稀便级、稀便率和腹泻指数；采用试剂盒测定小鼠肠道消化酶活力及炎症因子水平；采用高通量测序技术分析结肠内容物肠道菌群变化。结果 与对照组比较，模型组小鼠首次排便时间显著缩短（P<0.01），稀便级、稀便率和腹泻指数显著升高（P<0.01）；消化酶乳酸脱氢酶（LDH）、淀粉酶（AMS）和脂肪酶（LPS）活力显著降低（P<0.01）；炎症因子白细胞介素1β （IL-1β）、环氧化酶2 （COX-2）、细胞间黏附分子1 （ICAM-1）和肿瘤坏死因子α （TNF-α）水平显著升高（P<0.01）；肠道菌群α多样性Simpson指数显著升高（P<0.05）；肠道菌群β多样性差异较大；变形菌门、梭杆菌门、变形菌纲、梭杆菌纲、肠杆菌目、梭杆菌目、拟杆菌科、丹毒丝菌科、埃格特菌科和拟杆菌属丰度显著升高（P<0.01），Muribaculaceae和norank_f__Muribaculaceae丰度显著降低（P<0.01）。与模型组比较，甘草泻心汤高、低剂量组小鼠首次排便时间显著延长（P<0.05、0.01）、稀便率和腹泻指数显著降低（P<0.05、0.01），高剂量组稀便级显著降低（P<0.01）；高、低剂量组各消化酶活力显著回升（P<0.05、0.01）；高、低剂量组各炎症因子水平显著降低（P<0.05、0.01）；高剂量组Simpson指数显著降低（P<0.05），β多样性更趋近对照组，显著回调各优势物种丰度的显著性变化（P<0.05、0.01）。结论 甘草泻心汤对于伊立替康诱导的腹泻小鼠具有明显的治疗作用，可能是其通过调整腹泻小鼠肠道菌群实现。

Objective To investigate the effect of Gancao Xiexin Decoction on the gut microbiota of mice with chemotherapy-related diarrhea. Methods Mice were randomly divided into the control group, model group, loperamide group (positive drug, 0.4 mg·kg^-1), and high-and low-dose Gancao Xiexin Decoction (16.4 and 4.1 g·kg^-1) groups. The chemotherapy-associated diarrhea model was induced by ip injection of 55 mg·kg^-1 irinotecan for 4 d. The time of first defecation, dilute stool grade, dilute stool rate and diarrhea index were recorded. The intestinal digestive enzyme activity and inflammatory factor level of mice were measured by kits. The changes in gut microbiota of colonic contents were analyzed by high-throughput sequencing technology. Results Compared with the control group, the first defecation time of the model group mice was significantly shortened (P < 0.01), and the stool grade, stool rate, and diarrhea index were significantly increased (P < 0.01), the activities of digestive enzyme lactate dehydrogenase (LDH), amylase (AMS) and lipase (LPS) decreased significantly (P < 0.01), the level of inflammatory factor interleukin-1 β (IL-1β), cyclooxygenase 2 (COX-2), intercellular adhesion molecule 1 (ICAM-1) and tumor necrosis factor α (TNF-α) were significantly increased (P < 0.01), the Simpson index of gut microbiota α diversity significantly increased (P < 0.05), there were significant differences in diversity of gut microbiota β, the abundance of Pseudomonadota, Fusobacteria, Proteobacteria, Fusobacteria, Enterobacterales, Fusobacteriaceae, Bacteroidaceae, Erysipelotrichaceae, Egerteraceae and Bacteroides increased significantly (P < 0.01), the abundance of Muribaculaceae and norank_f__Muribaculaceae significantly decreased (P < 0.01). Compared with the model group, the first defecation time of Gancao Xiexin Tang high and low dose group was significantly prolonged (P < 0.05, 0.01), the loose stool rate and diarrhea index were significantly reduced (P < 0.05, 0.01), the high dose group had a significant decrease in loose stool grade (P < 0.01), the activity of digestive enzyme of high and low dose group increased significantly (P < 0.05, 0.01), the levels of various inflammatory factors of high and low dose group significantly decreased (P < 0.05, 0.01), the Simpson index of high dose group significantly decreased (P < 0.05), β diversity was closer to the control group, Simpson changes in the abundance of dominant species were significantly reversed in high dose group (P < 0.05, 0.01). Conclusion Gancao Xiexin Decoction has a significant therapeutic effect on irinotecan-induced diarrhea mice, and this effect may be achieved by its adjustment of gut microbiota in diarrhea mice.

R285.5

南京药学会-常州四药医院药学科研基金项目（2017YX007）