双歧杆菌联合左卡尼汀对菌群失调腹泻模型大鼠肠道菌群的影响  

Effects of Bifidobacterium Combined with L-carnitine on Intestinal Flora of Dysbacteriosis Diarrhea Model Rats

作　　者：王重娟 周锦妍[2] 王崇静 梁月琴[1] 朱瑜丹 王星星 李仲昆 WANG Chongjuan;ZHOU Jinyan;WANG Chongjing;LIANG Yueqin;ZHU Yudan;WANG Xingxing;LI Zhongkun(Dept.of Pharmacy,the Affiliated Yan'an Hospital of Kunming Medical University,Kunming 650051,China;Dept.of Pediatrics,the Affiliated Yan’an Hospital of Kunming Medical University,Kunming 650051,China;School of Pharmacy,Yunnan Xinxing Vocational College,Kunming 650501,China)

机构地区：[1]昆明医科大学附属延安医院药学部,昆明650051 [2]昆明医科大学附属延安医院儿科,昆明650051 [3]云南新兴职业学院药学院,昆明650501

出　　处：《中国药房》2021年第6期682-690,共9页China Pharmacy

基　　金：国家自然科学基金资助项目(No.82060744);云南省高层次卫生技术人才培养专项经费(No.L-201625);云南省科技厅-昆明医科大学基础研究联合专项[No.2018FE001(-086)]。

摘　　要：目的:研究双歧杆菌联合左卡尼汀对菌群失调腹泻模型大鼠肠道菌群的影响。方法:将30只SD大鼠随机分为空白对照组、模型组、益生菌组(双歧杆菌三联活菌肠溶胶囊70 mg/mL)、左卡尼汀组(左卡尼汀注射液50 mg/mL)和左卡尼汀+益生菌组(左卡尼汀注射液50 mg/mL+双歧杆菌三联活菌肠溶胶囊70 mg/mL)。除空白对照组外,其余各组大鼠均连续灌胃50 mg/mL克林霉素磷酸酯(2 mL/只,每天1次,连续4天)以建立菌群失调腹泻模型。实验第5天起进入恢复期,各给药组大鼠开始灌胃相应药物,空白对照组和模型组大鼠灌胃等体积生理盐水;灌胃体积均为1 mL/只,每天1次,连续给药7天。实验期间观察各组大鼠的一般情况;收集造模期结束时正常对照组和模型组大鼠的粪便以及恢复期末次给药后各组大鼠的粪便,分别进行肠道菌群基因组DNA提取与聚合酶链式反应扩增、文库构建和高通量测序,并对处理后的有效数据进行操作分类单元聚类、物种注释以及肠道菌群的Alpha和Beta多样性分析。结果:造模期结束时,与空白对照组比较,模型组大鼠开始出现1级和2级粪便,肠道菌群的多样性、丰富度以及肠道中厚壁菌门/拟杆菌门比值和乳杆菌属、双歧杆菌属和阿克曼氏菌属等益生菌的丰度均显著降低(P<0.05),而肠球菌属等致病菌的丰度显著升高(P<0.05)。恢复期结束时,与模型组比较,益生菌组、左卡尼汀组和左卡尼汀+益生菌组大鼠的活动量和粪便的形态、颜色恢复至正常,肠道菌群的多样性和丰富度差异均无统计学意义(P>0.05),但其肠道中乳杆菌属的丰度有一定提高,且左卡尼汀+益生菌组大鼠肠道中阿克曼氏菌属的丰度显著升高(P<0.05)。结论:双歧杆菌联合左卡尼汀虽对提高菌群失调腹泻模型大鼠肠道菌群的多样性和丰富度无显著效果,但能在一定程度上增加其肠道中益生菌的丰度。OBJECTIVE:To study the effects of Bifidobacterium combined with L-carnitine on intestinal flora of dysbacteriosis diarrhea model rats.METHODS:Totally 30 SD rats were randomly divided into blank control group,model group,probiotics group(Bifidobacterium triple viable enteric coated capsules 70 mg/mL),L-carnitine group(L-carnitine injection 50 mg/mL)and L-carnitine+probiotics group(L-carnitine injection 50 mg/mL+Bifidobacterium triple viable enteric coated capsules 70 mg/mL).Except for blank control group,the rats in other groups were given 50 mg/mL clindamycin phosphate intragastrically(2 mL/rat,once a day,for 4 consecutive days)to establish the model of dysbacteriosis diarrhea.On the 5 th day of the experiment,the rats in administration groups were given corresponding drugs intragastrically,blank control group and model group were given equal volume of normal saline intragastrically;with the dosage volume of 1 mL/rat,once a day,for consecutive 7 days.The general situation of rats in each group was observed during the experiment.The feces of normal control group and model group at the end of the modeling and the feces of the rats in administration group after the last administration were collected for genomic DNA extraction,polymerase chain reaction amplification,library construction and high-throughput sequencing.After processing,the effective data were analyzed by operational taxonomic unitsclustering and species annotation,as well as Alpha and Beta diversity of intestinal flora.RESULTS:At the end of the modeling,compared with blank control group,grade 1 feces and grade 2 feces were found in model group.The diversity and richness of intestinal flora,the ratio of Firmicutes/Bacteroidetes and the abundance of probiotics such as Lactobacillus,Bifidobacterium and Ackermann were significantly decreased(P<0.05),while the abundance of pathogenic bacteria such as Enterococcus was significantly increased(P<0.05).At the end of the recovery period,compared with model group,the activity,fecal morphology and color of rats in

关 键 词：肠道菌群 益生菌 左卡尼汀 双歧杆菌 高通量测序 多样性 

分 类 号：R963[医药卫生—微生物与生化药学] R372[医药卫生—药理学]