枯草杆菌二联活菌肠溶胶囊调节2型糖尿病合并昼夜节律紊乱小鼠糖脂代谢的作用机制

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Live combined Bacillus subtilis and Enterococcus faecium improves glucose and lipid metabolism in type 2 diabetic mice with circadian rhythm disruption via the SCFAs/ GPR43/GLP-1 pathway

HANRuimin1，ZHAOanke²，YUANJunfang³，SHI Zhenhong³，WANG Zhen2，WANGefeng

Scholofldofbeidt

AffiliatedHospitalofbeiniversityofngineering，Handan56oooina

Abstract：ObjectiveToinvestigatetheeffctsoflivecombinedBacillussubtilisandEnterococusfaecium（LCBE）onglucoseand lipid metabolism inmice withtype2diabetesmelitus（T2DM）andcircadian rhythm disorder（CRD）and explore the possible mechanisms. Methods KMmice wererandomized into normal diet （ND）group （n=8）， high-fat diet （HFD）group （n=8），and rhythm-intervention withHFDgroup （n=16）.After8 weeksoffeeding，the mice were givenanintraperitoneal injectionof streptozotocin （100mg/kg） to induce T2DM. The mice in CRD-T2DM group were further randomized into two equal groups for treatment with LCBE 225mg/kg） or saline by gavage; the mice in ND and HFD groups also received saline gavage for 8 weks.BloodcoselelofeeamesuedngcometensmevelsofallER2uliie andlipids were determinedwith ELISA.Colonmorphologyandhepaticlipid metabolismof themicewereexaminedusing HE stainingandOilRedOstaining，respectivelyandfecalshort-chainfattacids （SCAs）was detected using LC-MS;GPR43 andGLP-1expression levelswereanalyzed usingRT-qPCRand Western bloting.ResultsComparedwiththoseinCRDT2DM group，theLCBE-treatedmiceexibitedsgniicantbodyweightlo，loweredlevelsofER2，insulin，C-peptidetotal cholesterol （TC）andLDL-C，and increased levelsofBmalland HDL-Clevels.LCBE treatmentsignificantlyincreasedSCFAs， upregulated GPR43and GLP-1 expresions atboth the mRNAand proteinlevels，and improved hepatic steatosisand colon histology. Conclusion LCBEameliorates lipid metabolism disorder in CRD-T2DM mice by reducing body weight and improving lipid profiles and circadian regulators possibly via the SCFAs/GPR43/GLP-1 pathway.

Keywords：type2dabetesmelitus;circadianrhym;livecombinedBcilussubilisandEnterococusfaecium;short-aaty acids; glucolipid metabolism

2型糖尿病是一种常见的慢性代谢性疾病[1]，全球范围内患病率持续上升，预计到2030年糖尿病患者人数将增至6.43亿。（剩余13646字）