益生菌联合药食同源材料改善常用抗结核药所致小鼠肝损伤和肠道菌群紊乱的作用  

Effect of probiotics combined with food drug homologous products in ameliorating anti-tuberculous drugs-induced liver injury and intestinal dysbiosis in mice

作　　者：夏心怡 高良烽 宁茜茜 吴迪楠 李明[1] 李彧媛[1] 袁杰力[1] XIA Xin-yi;GAO Liang-feng;NING Xi-xi;WU Di-nan;LI Ming;LI Yu-yuan;YUAN Jie-li(Dalian Medical University,Dalian,Liaoning 116044,China;不详)

机构地区：[1]大连医科大学,辽宁大连116044

出　　处：《中国微生态学杂志》2022年第7期745-750,共6页Chinese Journal of Microecology

基　　金：国家自然科学基金(31900920)。

摘　　要：目的 探讨益生菌与药食同源材料补充对异烟肼、利福平、乙胺丁醇和吡嗪酰胺4种抗结核药联用所致小鼠肝损伤及肠道菌群紊乱的影响。方法 将30只SPF级雄性ICR小鼠随机分为对照组、模型组和治疗组,每组10只,其中模型组和治疗组小鼠给予4种抗结核药建立肝损伤模型,治疗组在此基础上给予益生菌联合药食同源材料组方。持续灌胃2周后每组随机抽取5只小鼠处死取材。剩余小鼠停止抗结核药灌胃,仅继续给予组方灌胃1周。检测血清中生化指标丙氨酸氨基转氨酶(ALT)、天冬氨酸氨基转移酶(AST)、三酰甘油(TG)、总胆固醇(TC)、总胆红素(TBiL)、尿酸(UA)及白蛋白(Alb)水平。采用流式细胞术分析各组5只小鼠脾脏免疫细胞亚群比例。提取结肠内容物DNA,采用16S rDNA测序分析各组肠道菌群构成。结果 益生菌联合药食同源材料可显著减轻抗结核药联用导致的小鼠ALT、AST、TC及TBiL水平的增加,同时缓解抗结核药联用导致的小鼠脾脏CD3^(+) T、CD4^(+) T细胞的减少。与模型组相比,治疗组小鼠肠道乳杆菌属和拟杆菌属相对丰度略有增加,葡萄球菌属相对丰度显著降低。第21天治疗组小鼠肠道菌群Alpha多样性与模型组相比显著增加。结论 益生菌联合药食同源材料对抗结核药联用所致的肝损伤及肠道菌群紊乱具有一定改善作用,且随干预时间的延长效果更明显。Objective To observe the effects of probiotics and food drug homologous(FDH) supplements on liver injury and intestinal dysbiosis in mice induced by four anti-tuberculous drugs: Isoniazid, Rifampin, Ethambutol and Pyrazinamide. Methods A total of 30 mice were randomly divided into a control group, a model group and a treatment group of 10 mice each. The model group and treatment group were given four kinds of anti-tuberculous drugs in combination to establish liver injury models, and the treatment group was additionally given probiotics combined with FDH products. 5 mice were randomly selected from each group after 2 weeks of gavage. The rest of the mice were given the products alone for 1 week after the gavage of anti-tuberculous drugs was stopped. The mice were killed on Days 14 and 21 respectively, and the serum levels of biochemical markers such as alanine aminotransferase(ALT), aspartate transaminase(AST), triglyceride(TG), total cholesterol(TC), total bilirubin(TBiL), uric acid(UA) and albumin(Alb) were measured. The proportion of immune cell subsets in the spleens of mice in each group was analyzed with flow cytometry. The colonic content DNA was extracted and the composition of gut microbiota was analyzed using 16 S rDNA sequencing. Results Probiotics combined with FDH products significantly lowered the increase of levels of AST, ALT, TC and TBiL, and alleviated the decrease of levels of CD3^(+)T and CD4^(+)T cells in spleen induced by anti-tuberculous drugs combination in mice. Compared with the model group, the relative abundances of Lactobacillus and Bacteroides in the treatment group increased slightly, while that of Staphylococcus decreased significantly. On the 21 st day, the alpha diversity of gut microbiota in the treatment group was significantly higher than that in the model group(P<0.05). Conclusion Probiotics combined with food drug homologous products can improve the liver injury and intestinal dysbiosis induced by anti-tuberculous drugs, and the effect is more obvious along with the time len

关 键 词：益生菌 药食同源 肝损伤 肠道菌群 抗结核药 

分 类 号：R575.5[医药卫生—消化系统]