Effects of Zuogui Jiangtang Tongmai Formula on glucolipid metabolism in type 2 diabetic rats based on intestinal flora and its metabolite SCFA
Objective To investigate the possible mechanism of Zuogui Jiangtang Tongmai Formula(ZGJTTMF)in the intervention of type 2 diabetes mellitus(T2DM)based on intestinal flora and short-chain fatty acid(SCFA)of the metabolites.Methods Twelve SD rats were selected as control group and fed with ordinary diet.Forty-eight rats were used as the modeling group,and a T2DM model was prepared by combining high-fat diet with streptozocin(STZ).After successful modeling,they were randomized into model(DM)group,low-dose(ZGJTTMF.L,12 g·kg-1)and high-dose(ZGJTTMF.H,24 g·kg-1)ZGJTTMF groups,and metformin 150 mg·kg-1+ atorvastatin 10 mg·kg-1(M.A)group.Drug intervention lasted for 4 weeks.Mental state,body mass,and random blood glucose of rats were monitored.The levels of serum insulin(INS),glycosylated hemoglobin(HbAlc),and inflammatory factors were measured by ELISA.The routine content of blood lipid was determined by biochemical analysis.HE staining was used to observe the pathological changes of colon.The intestinal flora structure was observed by 16SrRNA.Serum SCFA levels were examined by GC-MS.Results Compared with control group,DM group showed symptoms such as polydipsia,polyphagia,polyuria,and decreased body mass.In addition,blood glucose,INS,and HbAlc significantly increased(P<0.01).Moreover,the levels of total cholesterol(TC),triglyceride(TG),and low density lipoprotein cholesterol(LDL-C)increased,while high density lipoprotein cholesterol(HDL-C)significantly decreased(P<0.01).Besides,the levels of interleukin-1 β(IL-1β),interleukin-6(IL-6),and tumor necrosis factor-α(TNF-α)significantly increased(P<0.01).The lamina propria of the colon shows partial interruption and loss,with swelling cells and disordered villi.The relative abundance of Firmicutes and Proteobacteria,Enterobacteriaceae,and Escherichia Shigella increased in the DM group.In addition,the content of acetic acid and butyric acid in serum decreased(P<0.05,P<0.01).Compared with DM group,blood glucose,INS,and HbAlc in ZGJTTMF group significantly decreased(P<0.01).TC,TG,LDL-C also significantly decreased,while HDL-C significantly increased(P<0.01).The levels of IL-1β,IL-6,and TNF-α significantly decreased(P<0.01).Besides,colon cell swelling and inflammatory infiltration were relieved.The abundance of Bacteroidetes,Verrucobacteria,Lactobacillaceae,and Akkermansia increased.The content of butyric acid and acetic acid in serum increased(P<0.05,P<0.01).Conclusion ZGJTTMF may play a role in lowering blood glucose,stabilizing blood lipid,and alleviating inflammation by regulating intestinal flora and SCFA levels.