机构地区:[1]成都中医药大学临床医学院,四川成都610032 [2]北京中医药大学教育部中医养生学重点实验室 [3]北京中医药大学科技处 [4]北京中医药大学中医学院
出 处:《中国微生态学杂志》2025年第1期45-55,60,共12页Chinese Journal of Microecology
基 金:中医药防治糖尿病及其并发症学科创新引智基地(B20055)。
摘 要:目的探究绞股蓝对T2DM db/db小鼠肠道微生物群(GM)多样性、肠黏膜屏障功能及其对血糖水平的影响。方法选取4~5周龄的雄性db/m+小鼠作为正常对照组,对同龄的糖尿病模型雄性db/db小鼠随机分为模型组、二甲双胍组[0.20 g/(kg·d)]、绞股蓝组[0.78 g/(kg·d)],每组6只。药物干预持续5周,每周记录小鼠体重、饮水量和空腹血糖(FBG)情况,5周后检测FBG、糖化血清蛋白(GSP)和空腹血清胰岛素(FINS)、血清脂多糖(LPS)、二氧化铵(DAO)水平。小鼠结肠组织使用免疫组化染色技术检测小鼠结肠组织中紧密连接蛋白ZO-1和Occludin的表达水平及其分布特征。HE染色观察小鼠结肠的病理变化,同时收集小鼠结肠内粪便,应用16S rRNA基因测序技术检测各组小鼠粪便GM结构变化。结果与正常对照组比较,模型组小鼠体重、进食水量以及DAO、FBG、FINS、LPS、GSP水平均显著升高(F=119.392、84.719、9.979、72.573、58.599、2.894、8.462,P<0.001、<0.001、<0.010、<0.001、<0.001、<0.050、<0.050)。与模型组相比,二甲双胍可以显著改善小鼠的饮水量(F=84.719,P<0.050),显著降低小鼠体重、FBG、血清LPS、DAO水平(F=175.821、72.573、2.894、9.979,P<0.050、<0.001、<0.050、<0.001);二甲双胍可降低小鼠GSP水平,同时升高小鼠血清FINS水平,但差异均无统计学意义。与模型组比较,绞股蓝组可降低db/db小鼠饮水量,但差异无统计学意义;显著降低小鼠体重以及FBG、FINS、DAO、GSP水平(F=175.821、72.573、58.599、9.979、8.462,P<0.010、<0.001、<0.001、<0.001、<0.010);降低小鼠血清LPS水平,但差异无统计学意义;绞股蓝组GM有益菌的相对丰度增加。结论绞股蓝可以显著改善db/db糖尿病小鼠的糖代谢;可改善糖尿病小鼠GM丰度和肠黏膜屏障,保护肠道功能;可以显著改善糖尿病小鼠症状。Objective To explore the effects of Gynostemma pentaphyllum on intestinal microbiota(GM)diversity,intestinal mucosal barrier function and blood glucose level in T2DM db/db mice.Methods Male db/m+mice,aged 4 to 5 weeks,were selected as the normal control group.Concurrently,age-matched male db/db mice,a model for diabetes,were randomly allocated into three groups:a model group,a metformin treatment group[at a dose of 0.20 g/(kg·d)],and a Gynostemma pentaphyllum treatment group[at a dose of 0.78 g/(kg·d)],with six mice in each group.The drug intervention lasted for 5 weeks,during which time the body weight,water intake,and fasting blood glucose(FBG)levels of the mice were recorded on a weekly basis.At the conclusion of the 5-week period,the levels of FBG,glycosylated serum protein(GSP),fasting serum insulin(FINS),serum lipopolysaccharide(LPS),and diamine oxidase(DAO)were measured.Mouse colon tissue was used for immunohistochemical staining technology to observe the expression and distribution of tight junction proteins ZO-1 and Occludin,and hematoxylin-eosin(HE)staining to observe pathological changes in the mouse colon.Meanwhile,the stool in the colon of mice was collected and the GM structure of the stool of mice in each group was detected by 16S rRNA gene sequencing technology.Results Compared with the normal group,the model group showed significantly increased body weight,water intake,DAO,FBG,FINS,LPS,and GSP levels(F=119.392,F=84.719,F=9.979,F=72.573,F=58.599,F=2.894,F=8.462;P<0.001,P<0.001,P<0.010,P<0.001,P<0.001,P<0.050,P<0.050).Compared to the model group,metformin significantly reduced the water intake of the mice(F=84.719,P<0.050),as well as their body weight(F=175.821,P<0.050).When compared to the model group,metformin also significantly decreased FBG level in the mice(F=72.573,P<0.001),and notably lowered their serum LPS level(F=2.894,P<0.050),along with a significant reduction in DAO level(F=9.979,P<0.001).Although metformin decreased GSP level in the mice,the difference was not statistically signific
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