Effects Of Yixiaofang On Glucose And Lipid Metabolism In Patients With Diabetes And Fatty Liver And Its Mechanis

Type 2 diabetes mellitus(T2DM)and nonalcoholic fatty liver disease(NAFLD)co-exist as metabolic diseases with rapidly increasing prevalence,which make the current management strategy for T2DM with NAFLD remains difficult and complex.The current issues include lack of definitely pathogenesis and a concrete pharmacotherapy.Traditional Chinese medicine(TCM)can play a role to some extent in the treatment of metabolic diseases.Yi-Xiao Formula(YXF)created by my tutor was benefit for the treatment of T2DM in glucose and lipid metabolism.This study based on the preliminary research was to estimate the influence and pathogenesis of YXF in glucose and lipid metabolism among T2DM with NAFLD,in order to provide reference for clinical treatment.Objective:1.To observe the effect of YXF on glucose and lipid metabolism in KKAy mice of diabetes mellitus combined with nonalcoholic fatty liver disease and on TGF-β1/Smads signaling pathway in diabetic KKAy mice.2.To observe the therapeutic effect of YXF on T2DM with NAFLD patients whose TCM syndrome were deficiency of both qi and yin.Methods:1.In the experimental study,12-week-old KKAy mice were randomly divided into model group,TCM group and western medicine group.C57BL/6J mice were taken as control group.After 2 weeks of adaptive feeding,the TCM group was interfered by YXF,and the western medicine group was interfered by losartan,and the mice in control group and model group were given distilled water.The intervention period was 12 weeks.At 0,4,8 and 12 weeks after intervention,6 mice in each group were randomly selected and killed,to observe the changes of blood glucose,blood lipid,liver function and hepatic pathology by HE staining and oil red O staining.The levels of TGF-β1,Smad3,p-Smad3 and Smad7 in liver tissue were detected by Western blot and the mRNA levels of TGF-β1 and Smad7 were detected by RT-qPCR.2.In the clinical study,70 cases of T2DM with NAFLD of qi-yin deficiency syndrome were randomly divided into the control group and the experimental group.The control group was treated with basic therapy and the experimental group was treated with both YXF and basic therapy.The treatment period was 12 weeks.To observe the changes of TCM symptom score,blood glucose,blood lipid and liver transient elastography.All data were analyzed by SPSS26.0 software.Results:1.In the experimental study,KKAy mice were found to have significantly increased body weight,liver weight,liver weight index and increased levels of FBG,CHOL,HDL-C,LDL-C,AST(P<0.05).Compared with the model group,in TCM group,the body weight,liver weight and liver weight index were significantly decreased(P<0.05),and FBG was significantly decreased(P<0.01)at the 4th,8th and 12th weeks,and the levels of CHOL,TG,LDL-C and AST decreased after 8 weeks of intervention(P<0.05).In western medicine group,the levels of body weight,liver weight,liver weight index,FBG,ALT,AST,TG and HDL-C were not significantly improved(P>0.05),but the levels of CHOL and LDL-C were decreased(P<0.05)after 8 weeks of intervention.The scores of hepatic steatosis,lobular inflammation and balloon-like changes in KKAy mice were increased(P<0.05).Compared with the model group,the scores of hepatic steatosis decreased after 4-week intervention in TCM group(P<0.05)and the scores of lobular inflammation decreased after 12-week intervention in western medicine group(P<0.05).The results of oil red O staining showed that there were no red lipid droplets in the liver tissue of the control group,and there were a lot of red lipid droplets in the liver cells of the model group,and with the increasing of weeks,the red lipid droplets fused into sheets.Compared with the model group,the number of lipid droplets in TCM group decreased after 4 and 8 weeks of intervention,but there was no significant difference(P>0.05),and there was no significant change in western medicine group.WB showed that the expression of TGF-β1,Smad3,p-Smad3 and Smad7 were up-regulated in the model group,indicating the activation of TGF-β1/Smads signaling pathway in the liver issues.Compared with the model group,the expression of TGF-β1(P<0.01)and p-Smad3/Smad3(P<0.05)were significantly down-regulated after 12-week intervention in TCM group and western medicine group,and the expression of Smad7 was down-regulated in TCM group(P<0.01)but not in western medicine group(P>0.05).RT-qPCR showed that the expression of TGF-β1 mRNA and Smad7 mRNA in the model group was up-regulated(P<0.01).Compared with the model group,the expression of TGF-β1 mRNA and Smad7 mRNA in the liver issues were significantly down-regulated after 12-week intervention in TCM group and western medicine group(P<0.01).2.In the clinical study,there was no significant difference in baseline characteristics between the two groups(P>0.05),which indicated comparability.After treatment,the effective rate of the experimental group was higher than that of the control group(80%vs 57.14%,P<0.05),and the ineffective rate of the experimental group was significantly lower than that of the control group(5.71%vs 40%,P<0.01),and the overall effective rate of the experimental group was significantly higher than that of the control group(94.29%vs 60.00%,P<0.01).Compared with the control group,the total scores of TCM symptoms in the experimental group were significantly lower than those in the control group(17.03 vs 10.80,P<0.01).YXF significantly decreased the levels of FBG,TG,sdLDL-C and was superior to the control group in the aspects of lassitude,frequent urination,palpitation,insomnia and dry mouth(P<0.05)and the degree of CAP reduction was greater than that of the control group(P<0.05).Before and after treatment,the blood routine of the two groups were not abnormal and liver function(ALT,AST,GGT),renal function(BUN,SCR)had no significant change(P>0.05).Conclusions:1.YXF could significantly improve the obesity and glucose and lipid metabolism disorder of KKAy mice,regulate the expression of TGF-β1/Smads signaling pathway protein and gene,and alleviate hepatic steatosis.2.YXF can significantly improve the clinical symptoms of T2DM with NAFLD patients,improve glucose and lipid metabolism,which is worthy of further clinical application.