摘要
文章从胆汁酸代谢的角度研究驼乳源复合益生菌对血脂的调节作用及机制。8只db/m小鼠作为正常对照组,32只db/db糖尿病小鼠分为模型组,阳性药组,复合益生菌低、高剂量组,每组8只。检测血糖血脂相关基本生化指标,制作肝脏组织切片进行分析;超高效液相色谱-串联质谱分析仪(UPLC/MS-MS)检测胆汁酸谱的变化,实时荧光定量聚合酶链式反应(RT-PCR)和蛋白质印迹法检测胆固醇代谢相关基因及蛋白表达。结果表明,复合益生菌可以显著降低db/db小鼠血清中糖化血红蛋白、总胆固醇、甘油三酯和低密度脂蛋白胆固醇水平,减少肝脏脂肪变性,降低肝细胞内脂质空泡数量和体积;复合益生菌干预后,血清中总胆汁酸(TBA)降低,粪便中TBA升高,血清与粪便中初级胆汁酸(PBA)与次级胆汁酸(SBA)的比值降低;血清中游离胆汁酸占比升高,粪便中结合胆汁酸占比升高;胆汁酸中法尼醇X受体(FXR)及武田G蛋白偶联受体5(TGR5)的激动剂石胆酸(LCA)与鹅去氧胆酸(CDCA)含量升高,FXR的抑制剂牛磺-α-鼠胆酸(T-α-MCA)与牛磺-β-鼠胆酸(T-β-MCA)含量减少;复合益生菌干预后,小鼠肝脏中FXR表达增加,结肠中过氧化物酶体增殖物激活受体γ(PPARγ)与肝X受体α(LXRα)表达显著增加,胆固醇吸收蛋白NPC1样细胞内胆固醇转运蛋白1(NPC1L1)表达显著降低。因此复合益生菌可以改善db/db小鼠糖脂代谢,改善db/db小鼠胆汁酸组成结构,增加胆汁酸中FXR和TGR5的激动剂LCA与CDCA,减少胆汁酸中FXR的抑制剂T-α-MCA与T-β-MCA,促进FXR以及TGR5的表达,调节小鼠肝脏脂代谢;复合益生菌可能通过PPARγ-LXRα-NPC1L1通路,抑制肠道对胆固醇的吸收,调节脂代谢。
Department of Pharmacology,Xinjiang Medical University;State Key Laboratory of Natural Medicines;Xinjiang Uygur Autonomous Region Institute for Drug Control;NMPA Key Laboratory for Quality Control of Traditional Chinese(Uygur Medicine);Karamay Central Hospital;The aim of this study was to investigate the modulatory effects of composite probiotics from camel milk(CPCM)on blood lipids and their mechanisms from the perspective of bile acids metabolism.32 db/db diabetic mice were divided into a model group,a positive drug group,a composite probiotics low and high dose group,and 8 db/m mice as a normal control group.The basic biochemical indexes related to blood glucose and blood lipids were detected,and liver tissue sections were made for analysis;changes in bile acids profiles were detected by liquid chromatography-mass spectrometry hyphenation(LC-MS),and cholesterol metabolism-related genes and protein expression were detected by Real-time PCR and protein immunoblotting.CPCM significantly reduced serum levels of glycosylated haemoglobin,total cholesterol,triglycerides and LDL cholesterol,decreased hepatic steatosis,and reduced the number and volume of intracellular lipid vacuoles in hepatocytes in db/db mice.After the CPCM intervention,total bile acids(TBA)in serum decreased,TBA in faeces increased,the ratio of primary bile acids(PBA)to secondary bile acids(SBA)in both serum and faeces decreased;the percentage of free bile acids in serum increased,and the percentage of bound bile acids in faeces increased;the levels of farnesol X receptor(FXR)and agonists of Takeda G protein-coupled receptor 5(TGR5),Lithocholic acid(LCA)and Chenodeoxycholic acid(CDCA),in bile acids were increased,and FXR's inhibitors Tauro-α-muricholic acid(T-α-MCA)and Tauro-β-muricholic acid(T-β-MCA)decreased.Aftertheinterventionof CPCM,theexpressionof FXRincreasedintheliverofmice,theexpressionof peroxisomeproliferator-activated receptorγ(PPARγ)and liver X receptorα(LXRα)significantly increased in the colon,and the expression of cholestero
作者
迪黛尔·贾尔肯
塔布斯·马那尔
沈芳
库尔旦·胡达依别尔根
马嘉宁
新华·那比
Didaier Jiaerken;Tabusi Manaer;SHEN Fang;Kuerdan Hudayibieergen;MA Jianing;Xinhua Nabi(Department of Pharmacology,Xinjiang Medical University,Urumqi 830054,China;State Key Laboratory of Natural Medicines,Urumqi 830017,China;Xinjiang Uygur Autonomous Region Institute for Drug Control,Urumqi 830004,China;NMPA Key Laboratory for Quality Control of Traditional Chinese(Uygur Medicine),Urumqi 830054,China;Karamay Central Hospital,Karamay 834000,China)
出处
《中国乳品工业》
CAS
北大核心
2024年第6期5-16,共12页
China Dairy Industry
基金
国家自然科学基金项目(82260640)。
关键词
驼乳源复合益生菌
2型糖尿病
胆汁酸
脂代谢
胆固醇
NPC1L1
composite probiotics from camel milk(CPCM)
type 2 diabetesbile acids
lipid metabolism
cholesterol
NPC1L1
