益生菌调节肠道菌群对糖尿病并发抑郁症大鼠血糖及抑郁样行为的影响  

Effects of probiotics on blood glucose and depression-like behavior in rats with diabetes-related depression by regulating gut microbiota

作　　者：雷诗卉 李薇[1] 杨蕙[1] 王瑾茜 袁霞红 Shihui Lei;Wei Li;Hui Yang;Jinxi Wang;Xiahong Yuan(Medical Innovation Experimental Center,First Hospital of Hunan University of Chinese Medicine,Changsha 410000,China;First Clinical College of Traditional Chinese Medicine,Hunan University of Chinese Medicine,Changsha 410000,China)

机构地区：[1]湖南中医药大学第一附属医院医学创新实验中心,长沙410000 [2]湖南中医药大学第一中医临床学院,长沙410000

出　　处：《中华糖尿病杂志》2022年第12期1453-1460,共8页CHINESE JOURNAL OF DIABETES MELLITUS

基　　金：湖南省自然科学基金(2019JJ50467);湖南省中医药科研计划项目(D2022099);湖南省卫健委科研计划课题(C2019091)。

摘　　要：目的探讨益生菌调节肠道菌群对糖尿病并发抑郁症大鼠血糖及抑郁样行为的影响。方法将24只大鼠分为正常对照组、糖尿病并发抑郁症(DD)组和益生菌组,每组8只。通过高脂饮食结合腹腔注射链脲佐菌素(每只60 mg/kg)诱导,给予慢性不可预计温和应激(CUMS)刺激28 d建立DD大鼠模型,同时给予益生菌(双歧杆菌联合乳酸菌)重建其肠道菌群。每周称量大鼠体重的同时进行空腹血糖(FPG)检测,采用强迫游泳实验和矿场实验检测各组大鼠抑郁样行为,采用酶联免疫吸附测定法检测促炎性细胞因子[白细胞介素-1β(IL-1β)、白细胞介素-6(IL-6)和肿瘤坏死因子-α(TNF-α)]、下丘脑-垂体-肾上腺轴(HPA)相关蛋白[促肾上腺皮质激素释放激素(CRH)、促肾上腺皮质激素(ACTH)和皮质醇]及脂多糖(LPS)在血清中的含量;采用16s rRNA对各组大鼠肠道内容物微生物菌群进行测序分析。两组之间比较采用独立样本t检验,多组之间比较采用单因素或双因素方差分析。结果与对照组比较,DD组大鼠FPG升高并表现出明显抑郁样行为(静止时间增加、水平活动降低)和HPA亢进[功能相关的蛋白(CRH、ACTH和皮质醇)均升高],且血清中LPS及促炎性细胞因子(IL-1β、IL-6和TNF-α)含量均升高,差异均有统计学意义(P<0.05)。与DD组相比,益生菌组大鼠FPG降低,LPS及促炎性细胞因子含量明显降低,同时抑郁样行为和HPA亢进明显缓解,差异均有统计学意义(P<0.05)。16s rRNA肠道菌群测序提示,各组大鼠肠道菌群α多样性无明显差异,β多样性存在差异;厚壁菌门和拟杆菌门为大鼠肠道菌群的主要菌种,其次为变形菌门和放线菌门;与对照组比较,DD组6个科[瘤胃球菌科_UCG-005(Ruminococcaceae_UCG-005)、瘤胃球菌科_UCG-013(Ruminococcaceae_UCG-013)、瘤胃梭菌科(Ruminiclostridium)、颤杆菌克科(Oscillibacter)、脱硫弧菌科(Desulfovibrionaceae)和普雷沃菌科(Prevotellaceae)]的丰度�Objective To explor the effects of probiotics on blood glucose and depression-like behaviors in rats with diabetes-related depression by regulating gut microbiota.Methods Twenty-four rats were divided into a control group,a diabetes-related depression(DD)group and a probiotic group,with eight rats in each group.A rat model of DD was established by a high-fat diet combined with stretozotocin(60 mg/kg per rat)and chronic unpredictable mild stress(CUMS)stimulation for 28 days,while probiotics were administered to rebuild their gut microbiota.Fasting plasma glucose(FPG)testing was performed at the same time as the weekly weighing.The depressive behaviors were tested by forced swimming and open field experiments;detection of serum levels of pro-inflammatory cytokines[interleukin-1β(IL-1β),interleukin-6(IL-6),tumor necrosis factor-α(TNF-α)],hypothalamic-pituitary-adrenal axis(HPA)-related proteins[corticotropin releasing hormone(CRH),adreno cortico tropic hormone(ACTH)and Cortisol],and lipopolysaccharide(LPS)were tested by enzyme-linked immunosorbent assay(ELISA);the intestinal contents of each group were collected,sequenced by 16s rRNA analyze.Independent sample t-test was used for comparison between the two groups,and one-way or two-way analysis of variance(ANOVA)was used for comparison between multiple groups.Results Compared with the control group,the DD group had elevated FPG and showed significantly increased depression-like behavior(increased resting time and decreased horizontal activity in rats)and hyper-HPA[function-related proteins(CRH,ACTH and cortisol)were elevated],and serum levels of LPS and pro-inflammatory cytokines(IL-1β,IL-6 and TNF-α)were elevated,all with statistically significant differences(P<0.05).Compared with the DD group,the probiotic group showed lower FPG and significantly lower LPS and pro-inflammatory cytokine levels,while depression-like behavior(increased resting time and reduced horizontal activity)and HPA hyperactivity were significantly alleviated,and the differences were stati

关 键 词：糖尿病 抑郁症 肠道菌群 益生菌 16s rRNA 

分 类 号：R587.2[医药卫生—内分泌] R749.4[医药卫生—内科学]