[1]廖红梅,李霞,花红燕.乳酸菌混合物通过激活胆汁酸-TGR5-GLP-1轴改善糖尿病肥胖小鼠血糖及肠道屏障功能实验研究[J].陕西医学杂志,2026,(3):299-304,311.[doi:DOI:10.3969/j.issn.1000-7377.2026.03.002]
　LIAO Hongmei,LI Xia,HUA Hongyan.Lactic acid bacteria mixture improves blood glucose and intestinal barrier function in diabetic obese mice by activating bile acid-TGR5-GLP-1 axis[J].,2026,(3):299-304,311.[doi:DOI:10.3969/j.issn.1000-7377.2026.03.002]
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乳酸菌混合物通过激活胆汁酸-TGR5-GLP-1轴改善糖尿病肥胖小鼠血糖及肠道屏障功能实验研究

《陕西医学杂志》[ISSN:1000-7377/CN:61-1281/TN]

卷:
期数:
2026年3期
页码:
299-304,311
栏目:
基础研究
出版日期:
2026-03-05

文章信息/Info

Title:
Lactic acid bacteria mixture improves blood glucose and intestinal barrier function in diabetic obese mice by activating bile acid-TGR5-GLP-1 axis
作者:
廖红梅; 李霞; 花红燕
（宁夏回族自治区第二人民医院 固原市人民医院普儿科，宁夏 固原 756000）
Author(s):
LIAO Hongmei; LI Xia; HUA Hongyan
(Department of General Pediatrics,the Second People’s Hospital of Ningxia Hui Autonomous Region,Guyuan 756000,China)
关键词:
肥胖; 糖尿病; 乳酸菌混合物; 胆汁酸-G蛋白偶联胆汁酸受体5-胰高血糖素样肽1轴; 肠道屏障功能; 血糖; 小鼠
Keywords:
besity; Diabetes; Lactic acid bacteria mixture; Bile acid-TGR5-GLP-1 axis; Intestinal barrier function; Blood glucose; Mouse
分类号:
R -33
DOI:
DOI:10.3969/j.issn.1000-7377.2026.03.002
文献标志码:
A
摘要:
目的：基于胆汁酸-G蛋白偶联胆汁酸受体5（TGR5）-胰高血糖素样肽1（GLP-1）轴探究乳酸菌混合物对糖尿病肥胖小鼠血糖及肠道屏障功能的影响。方法：将C57BL/6J小鼠随机分为对照组（12只）、模型组（14只）、阳性药物二甲双胍组（14只）、乳酸菌混合物组（14只）。高脂饲料饲养及链脲佐菌素腹腔注射构建糖尿病肥胖小鼠模型。检测各组小鼠体重、空腹血糖、血清胰岛素与总胆汁酸水平；实时荧光定量PCR（RT-qPCR）及蛋白质印迹（Western blot）检测结肠组织中TGR5、GLP-1 mRNA及蛋白的表达；免疫组织化学染色检测胰腺组织中GLP-1受体（GLP-1R）蛋白的表达；HE染色检测结肠组织的病理学变化；Western blot检测结肠组织中闭锁小带蛋白1（ZO-1）、闭合蛋白-1（Claudin-1）、咬合蛋白（Occludin）的表达。结果：与对照组比较，模型组小鼠体重、空腹血糖升高（均P<0.05），胰岛素、总胆汁酸、TGR5、GLP-1、GLP-1R、ZO-1、Claudin-1、Occludin水平降低（均P<0.05），结肠组织水肿，且有大量炎症细胞浸润。与模型组比较，阳性药物组小鼠体重、空腹血糖降低（均P<0.05），总胆汁酸、TGR5、GLP-1、ZO-1、Claudin-1、Occludin水平升高（均P<0.05），结肠组织水肿及炎症细胞浸润情况减轻；乳酸菌混合物空腹血糖降低（P<0.05），总胆汁酸、胰岛素、TGR5、GLP-1、GLP-1R、ZO-1、Claudin-1、Occludin水平升高（均P<0.05），结肠组织水肿及炎症细胞浸润情况减轻。结论：乳酸菌混合物能够通过激活胆汁酸-TGR5-GLP-1轴来降低糖尿病肥胖小鼠血糖，并改善其肠道屏障功能。
Abstract:
Objective:To investigate the effects of lactic acid bacteria mixture on blood glucose and intestinal barrier function in diabetic obese mice based on the bile acid-G protein-coupled bile acid receptor 5 (TGR5)-glucagon-like peptide 1 (GLP-1) axis.Methods：The C57BL/6J mice were randomly divided into control group (12 mice),model group (14 mice),metformin positive drug group (14 mice),and lactic acid bacteria mixture group (14 mice).The diabetes-obesity mouse model was constructed by feeding with high-fat diet and intraperitoneal injection of streptozotocin.The body weight,fasting blood glucose,serum insulin and total bile acid levels of each group were detected;RT-qPCR and Western blot were used to detect the expression of TGR5 and GLP-1 mRNA and protein in the colon tissue;immunohistochemical staining was used to detect the expression of GLP-1 receptor (GLP-1R) protein in the pancreatic tissue;HE staining was used to detect the pathological changes of the colon tissue;Western blot was used to detect the expression of ZO-1,Claudin-1 and Occludin proteins in the colon tissue.Results:Compared with the control group,the body weight and fasting blood glucose of the model group increased (all P<0.05),while the levels of insulin,total bile acid,TGR5,GLP-1,GLP-1R,ZO-1,Claudin-1,and Occludin decreased (all P<0.05),and the colon tissue showed edema,and there was a large infiltration of inflammatory cells.Compared with the model group,the positive drug group had decreased body weight and fasting blood glucose (all P<0.05),while the levels of total bile acid,TGR5,GLP-1,ZO-1,Claudin-1,and Occludin increased (all P<0.05),and the edema and inflammatory cell infiltration in the colon tissue were alleviated;the fasting blood glucose of the lactic acid bacteria mixture group decreased (P<0.05),and the levels of total bile acid,insulin,TGR5,GLP-1,GLP-1R,ZO-1,Claudin-1,and Occludin increased (all P<0.05),and the edema and inflammatory cell infiltration in the colon tissue were alleviated.Compared with the positive drug group,the mice in the lactic acid bacteria mixture group had decreased fasting blood glucose (P<0.05),and the levels of total bile acid,TGR5,GLP-1,ZO-1,Claudin-1,and Occludin increased (all P<0.05),and had further reduced colonic tissue edema and infiltration of inflammatory cells.Conclusion:The lactic acid bacteria mixture reduces blood glucose and improves the intestinal barrier function of diabetic obese mice by activating the bile acid-TGR5-GLP-1 axis.

参考文献/References:

[1]魏雪乔,张建影,黄娟,等.基于SIRT1/PGC-1α通路探讨黄芪补肾活血汤对糖尿病肾病大鼠的保护作用及机制[J].陕西中医,2025,46(8):1036-1041.
[2]吴悠,陈源,胡耀木,等.滋肾丸对db/db糖尿病模型小鼠肠道屏障功能及骨骼肌转录组的影响[J].中国实验方剂学杂志,2023,29(16):22-32.
[3]高飞,龚文品,葛敬芳.复合乳酸菌胶囊联合叶酸对小儿腹泻病肠道菌群、肠黏膜屏障功能影响[J].中国中西医结合消化杂志,2022,30(1):69-72.
[4]赵聪瑞,史晓丹,吕文晴,等.复合乳酸菌对氨苄西林诱导小鼠腹泻缓解作用[J].食品研究与开发,2024,45(19):13-20.
[5]王胜男.基于BA-TGR5-GLP-1途径探讨半夏泻心汤治疗T2DM的作用机制[D].成都:成都中医药大学,2022.
[6]FUNAYAMA T,NOZU T,ISHIOH M,et al.Centrally administered GLP-1 analogue improves intestinal barrier function through the brain orexin and the vagal pathway in rats[J].Brain Res,2023,1809：148371.
[7]张淑芹,李彦杰,秦合伟,等.基于AMPK信号通路探讨参苓白术散改善肥胖型2型糖尿病小鼠的作用机制[J].中药材,2022,45(11):2737-2742.
[8]赵芸慧,梁永林,朱向东,等.参七糖络丸调控PI3K/Akt通路改善肥胖型糖尿病小鼠肝细胞凋亡的机制研究[J].中国现代应用药学,2025,42(6):905-912.
[9]曹云婷,王玮.绿茶调节Nesfatin-1、Ghrelin表达对肥胖小鼠糖脂代谢及体重的影响实验研究[J].陕西医学杂志,2025,54(9):1189-1196.
[10]高泽林,杨淑彬.艾塞那肽与沙格列汀分别联合二甲双胍治疗腹型肥胖2型糖尿病疗效及安全性对比研究[J].陕西医学杂志,2024,53(9):1240-1244.
[11]李晓芬,杨洲,权金星,等.基于2型糖尿病肥胖小鼠模型探究维生素D对脂肪组织铁死亡的影响[J].中国现代医学杂志,2025,35(13):24-29.
[12]杨晓华,洪嘉淇,王临好,等.降糖活性乳酸菌的筛选及对2型糖尿病小鼠的改善作用[J].食品科学,2025,46(8):151-161.
[13]申思月.抗肥胖乳酸菌的筛选及其对肥胖小鼠的减肥作用[D].哈尔滨:哈尔滨工业大学,2023.
[14]王灵叶,杨晗,葛胜祥,等.DNA甲基化在2型糖尿病治疗中的研究进展[J].生命科学,2023,35(7):925-934.
[15]宋美芳.从胆汁酸-TGR5-GLP-1通路探讨抑郁模型大鼠糖代谢异常及逍遥散的作用机理[D].北京:北京中医药大学,2019.
[16]刘万,梁菲,蔡铁全,等.小檗碱和肉桂多酚联合使用可通过Bas-TGR5-GLP-1改善T2DM大鼠的葡萄糖代谢[J].药学学报,2024,59(1):135-142.
[17]SEPEHR A,AGHAMOHAMMAD S,GHANAVATI R,et al.Role of native probiotic lactobacillus species via TGF-β signaling pathway modulation in CRC[J].Iran Biomed J,2024,28(4):168-178.
[18]王艳明.基于肠道菌群探讨乳源性复合益生菌诱导结肠GLP-1分泌及M2极化的分子机制研究[D].乌鲁木齐:新疆医科大学,2020.
[19]HERSOUG L G,MOLLER P,LOFT S.Role of microbiota-derived lipopolysaccharide in adipose tissue inflammation,adipocyte size and pyroptosis during obesity[J].Nutr Res Rev,2018,31(2):153-163.
[20]HUANG J,GUAN B,LIN L,et al.Improvement of intestinal barrier function,gut microbiota,and metabolic endotoxemia in type 2 diabetes rats by curcumin[J].Bioengineered,2021,12(2):11947-11958.
[21]马丽,曹昕昱,陶枫,等.番泻苷A通过减少mtROS保护肠道屏障功能治疗2型糖尿病的机制研究[J/OL].辽宁中医杂志,1-13[2025-09-28].https://link.cnki.net/urlid/21.1128.R.20250716.1913.067.
[22]张远,张钟友,冯慧琳,等.四妙丸通过调节肠道菌群改善大鼠肠道屏障功能并上调ABCG2表达促进回肠排泄尿酸[J].中国实验方剂学杂志,2026,32(1):101-112.
[23]XIAO Y,YAP J A,ONG Z Y.Effects of glucagon-like peptide 1 receptor signaling in the dorsolateral septum on ethanol operant self-administration and relapse behaviors[J].Neuropharmacology,2025,279:110640.
[24]HAN H S,HWANG S,CHOI S Y,et al.Roseburia intestinalis-derived extracellular vesicles ameliorate colitis by modulating intestinal barrier,microbiome,and inflammatory responses[J].J Extracell Vesicles,2024,13(8):e12487.
[25]肖金华,戴振宇,邓宸玺,等.乳酸菌分离鉴定及其对雏鸡肠道屏障功能的影响[J].江西畜牧兽医杂志,2024,43(5):19-22.
[26]吴菊华.乳酸菌对脓毒症大鼠肠道屏障功能的保护作用[D].福州:福建医科大学,2018.

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备注/Memo

备注/Memo:
宁夏回族自治区自然科学基金资助项目（2023AAC01395）
更新日期/Last Update: 2026-03-05