基于肠道菌群维生素K_(2)调控肝脏胰岛素抵抗作用机制  

Vitamin K_(2) alleviates insulin resistance based on gut microbiota

作　　者：宋婷 李佳 张茜 苏向妮 SONG Ting;LI Jia;ZHANG Qian;SU Xiangni(Department of Fundamental Medicine,Air Force Medical University,Xi'an,Shaanxi 710032,China;不详)

机构地区：[1]空军军医大学基础医学院,陕西西安710032 [2]空军军医大学护理系

出　　处：《中国微生态学杂志》2024年第10期1117-1122,共6页Chinese Journal of Microecology

基　　金：国家自然科学基金青年科学基金项目(82103810);陕西省重点研发计划一般项目(2023-YBSF-254)。

摘　　要：目的 探讨维生素K_(2)(VK_(2))改善小鼠肝脏胰岛素抵抗(IR)的作用是否与肠道菌群有关。方法 将50只4~5周龄、体重14~15 g的C57BL/6J雄性小鼠随机分为正常饮食组(n=10)和高脂饮食(HFD)组(n=40),采用HFD持续喂养16周诱导肥胖建立IR模型,模型建立成功后给予VK_(2)进行干预,干预结束后检测小鼠空腹血糖耐量(IPGTT)、胰岛素耐量(ITT)及空腹胰岛素(FINS)和血糖(FBG)水平等指标,采用16S r RNA基因测序检测各组小鼠粪便肠道微生物;为进一步明确VK_(2)与肠道菌群的作用,采用抗生素鸡尾酒法持续14 d喂养HFD诱导肥胖小鼠,清扫肠道菌群模拟无菌小鼠,运用菌群移植实验(FMT)将VK_(2)处理组小鼠粪便混悬液通过灌胃移植入无菌HFD小鼠体内,持续灌胃14 d,结束后检测各组小鼠IR相关指标,肝、肠组织进行油红O染色和HE染色,观察其病理形态。结果 ANOVA方差分析显示,与正常饮食组比较HFD组小鼠IPGTT、ITT曲线下面积以及FBG、FINS水平均显著增加,VK_(2)干预后小鼠IPGTT、ITT曲线下面积以及FBG、FINS水平均显著降低(均P<0.05)。16S rRNA基因测序检测结果显示,VK_(2)干预后肥胖小鼠肠道菌群组成在属水平发生了显著变化,表现为Faecalibacterium、 Bifidobacterium、 Pseudogracilibacilus等菌群丰度显著增加。Spearman相关性分析显示,FBG、FINS水平及HOMA-IR指数与Bifidobacterium显著相关(均P<0.05)。抗生素处理的无菌小鼠(Atb+VK_(2))组给予VK_(2)干预后,小鼠体重、空腹FBG、FINS水平均未出现改善,而VK_(2)干预无菌小鼠同时给予粪便移植(Atb+FTM)组小鼠的体重、空腹FBG、FINS水平与HFD组相比均显著降低(均P<0.05),组织病理检测结果也显示VK_(2)干预组和Atb+FTM组小鼠肝脏脂滴减少、肠黏膜形态紊乱改善,炎症因子水平显著降低(均P<0.05)。结论 VK_(2)具有改善肥胖小鼠IR作用,该作用与其改善肥胖小鼠肠道菌群紊乱,减轻肠道通透性和炎症因子有关。Objective To explore the role of Vitamin K_(2) in improving hepatic insulin resistance(IR) based on gut microbes in mice.Methods C57BL/6J male mice(4 to 5 weeks old) were housed in a room with a 12-12 h light-dark cycle and temperature of 23 ℃±2 ℃ to establish IR mouse model.After adaptation to the new environment for 1 week,the animals were randomly and equally divided into four groups.Clinical indicators of IR including body weight,fasting insulin,oral glucose tolerance test(OGTT),insulin tolerance test(ITT) and HOMA-IR index were examined.16S rRNA gene sequencing was performed by Majorbio Biotechnology Co.,Ltd.Results The body weight,fasting insulin,OGTT,ITT and HOMA-IR index of the HFD-fed mice significantly elevated compared with control mice(all P<0.05),indicating severe glucose intolerance and IR in HFD-fed mice.The Vitamin K_2-treated group showed significant decrease in fluid and fat mass(all P<0.05),but the treated group showed no significant difference in mass change compared with the HFD group.After Vitamin K_(2) intervention,the AUCs of IPGTT and ITT,and HOMA-IR index lowered,indicating a significant improvement in glucose tolerance and insulin sensitivity(all P<0.05).Overall,the above results indicated that Vitamin K_(2had) a beneficial effect that ameliorates glucose metabolism disorders in HFD-induced obesity mice.The relative abundance of gut microbes showed that Faecalibacterium,Bifidobacterium and Pseudogracilibacilus were enriched in the gut microbiota of mice with Vitamin K_(2) supplementation at the genus level.Compared with HFD group and Vitamin K_(2) group,the abundances of Bifidobacterium,Pseudogracilibacillus and Dubosiella significantly increased in Vitamin K_2-supplemented group.Conclusion Vitamin K_(2) has the effect of improving insulin resistance in obese mice.This effect is related to the improvement of intestinal microbiota disorders,increased abundance of beneficial bacteria,and reduced intestinal permeability and inflammatory factors in obese mice.The intestinal Bifidobacte

关 键 词：维生素K_(2) 胰岛素抵抗 肠道菌群 双歧杆菌 

分 类 号：R153.3[医药卫生—营养与食品卫生学]