目的 研究甘草瀉心湯對(duì)化療相關(guān)腹瀉小鼠腸道菌群的影響。方法 將小鼠隨機(jī)分為對(duì)照組、模型組、洛哌丁胺（陽(yáng)性藥，0.4 mg·kg^-1）組和甘草瀉心湯高、低劑量（16.4、4.1 g·kg^-1）組；采用連續(xù)4 d ip 55 mg·kg^-1伊立替康誘導(dǎo)小鼠化療相關(guān)腹瀉模型；記錄小鼠首次排便時(shí)間、稀便級(jí)、稀便率和腹瀉指數(shù)；采用試劑盒測(cè)定小鼠腸道消化酶活力及炎癥因子水平；采用高通量測(cè)序技術(shù)分析結(jié)腸內(nèi)容物腸道菌群變化。結(jié)果 與對(duì)照組比較，模型組小鼠首次排便時(shí)間顯著縮短（P<0.01），稀便級(jí)、稀便率和腹瀉指數(shù)顯著升高（P<0.01）；消化酶乳酸脫氫酶（LDH）、淀粉酶（AMS）和脂肪酶（LPS）活力顯著降低（P<0.01）；炎癥因子白細(xì)胞介素1β （IL-1β）、環(huán)氧化酶2 （COX-2）、細(xì)胞間黏附分子1 （ICAM-1）和腫瘤壞死因子α （TNF-α）水平顯著升高（P<0.01）；腸道菌群α多樣性Simpson指數(shù)顯著升高（P<0.05）；腸道菌群β多樣性差異較大；變形菌門、梭桿菌門、變形菌綱、梭桿菌綱、腸桿菌目、梭桿菌目、擬桿菌科、丹毒絲菌科、埃格特菌科和擬桿菌屬豐度顯著升高（P<0.01），Muribaculaceae和norank_f__Muribaculaceae豐度顯著降低（P<0.01）。與模型組比較，甘草瀉心湯高、低劑量組小鼠首次排便時(shí)間顯著延長(zhǎng)（P<0.05、0.01）、稀便率和腹瀉指數(shù)顯著降低（P<0.05、0.01），高劑量組稀便級(jí)顯著降低（P<0.01）；高、低劑量組各消化酶活力顯著回升（P<0.05、0.01）；高、低劑量組各炎癥因子水平顯著降低（P<0.05、0.01）；高劑量組Simpson指數(shù)顯著降低（P<0.05），β多樣性更趨近對(duì)照組，顯著回調(diào)各優(yōu)勢(shì)物種豐度的顯著性變化（P<0.05、0.01）。結(jié)論 甘草瀉心湯對(duì)于伊立替康誘導(dǎo)的腹瀉小鼠具有明顯的治療作用，可能是其通過調(diào)整腹瀉小鼠腸道菌群實(shí)現(xiàn)。

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

南京藥學(xué)會(huì)-常州四藥醫(yī)院藥學(xué)科研基金項(xiàng)目（2017YX007）