| Objective: To investigate the influence of glucose and lipid metabolism by stasis-dissipating and phlegm-removing method of Dan-gua Fang in type2diabetes patients and experimental animals including high-fat fed diabetic GK rats and STZ induced diabetic ApoE-/-mice, discuss part of the mechanism about improving glucose and lipid metabolism.Methods:â‘ 74type2diabetes patients meeting to the inclusion criteria were randomly assigned to two groups. Under diet and exercise, patients in the control group were given conventional antidiabetic, antihypertensive, lipid lowering and anti-platelet therapy, etc, whereas above mentioned routine treatment, patients in the treatment group plus Dan-gua Fang. Two months after treatment, the changes of blood glucose, blood lipids, body weight, Four liver fibrosis indicators, TCM syndrome, and symptom scores and clinical efficacy were observed.â‘¡13-week-old diabetic GK rats were randomly divided into four groups (10rats per group), DGF, MET, MOD, and SIM group, while another ten Wistar rats were set to NOR group. Four groups of GK rats ate high-fat diet freely, and had relative pharmacological intervention, whereas rats in NOR group were fed with normal diet. After twenty-four weeks, the liver expression of SIRT1-LKB1-AMPK mRNA and protein expression were detected. Histomorphology of liver tissue stained was observed by HE. Blood glucose (BG), glycosylated hemoglobin (HbAlc), food intake, body weight, Adiponectin (APN), phosphorylated acetyl coenzyme A carboxylase (pACC) and Alanine aminotransferase (ALT) of each group rats were also detected.â‘¢8-week-old diabetic ApoE-/-mice were randomly divided into four groups:MOD, DGF, TZD and D+T group, while another C57BL/6J mice were set to C57group. ApoE-/-mice were injected with STZ to induce diabetes model, and had relative pharmacological intervention. After12weeks, the liver mRNA and protein expression of Adiponectin Receptor2(AdipoR2) and Leptin Receptor (OB-Rb) were detected. Histomorphology of liver tissue stained was observed by HE, Masson and Red Oil O. BG, HbAlc, food intake, body weight of each group rats were also detected.Result:â‘ After intervention, in both control and treated groups, FBG,2hBG,and HbAlc were significantly decreased compared with before treatment (P<0.01), compared with control group after treatment, FBG, and HbAlc were significantly lower in treated group (P<0.05). In both control and treated groups, TC, TG, and LDL-c, were significantly decreased compared with before treatment (P<0.01), compared with control group after treatment, TC, TG, and LDL-c were significantly lower in treated group (P<0.05). Hyaluronic acid, Laminin, â…¢ procollagen protein and â…£ collagen protein in treatment group were significantly were lower than in control group. After treatment, symptom scores decreased in both two groups compared with before treatment (P<0.01), and symptom scores in treated group was lower than in control group (P<0.01). Total clinical efficacy in treated group were higher than in control group (P<0.01).â‘¡Dan-gua Fang can moderately control food intake and body weight of GK rats. Dan-gua Fang could obviously control FBG, Random blood glucose (RBG). In the reduction of FBG, Dan-gua Fang was comparatively equivalent to Metformin. And in the reduction of RBG, Dan-gua Fang was slightly inferior to Metformin. Dan-gua Fang had better effect on reducing TC, TG and LDL-c, improving HDL-c, superior to MET and SIM group significantly. Dan-gua Fang could promote the expression of SIRT1-LKB1-AMPK mRNA and especially the protein expression of AMPKa in liver, which was apparently higher than that in other GK rats. Dan-gua Fang could increase serum APN and pACC concentration and was able to decrease the serum ALT significantly. It also could effectively improve the pathological changes in GK rats liver than Metformin and Simvastatin, such as ectopic fat deposition, degeneration, inflammation and necrosis.â‘¢Dan-gua Fang could moderately control body weight of ApoE-/-mice. Dan-gua Fang could obviously decrease BG, HbAlc, TC and LDL-c. Dan-gua Fang could promote the mRNA expression of AdipoR2in liver in DGF group than in MOD group (P<0.01), and superior to TZD group (P<0.05). Dan-gua Fang also could promote the protein expression of AdipoR2and decrease the protein expression of OB-Rb in liver in DGF group than in MOD group (P<0.01), and superior to D+T and TZD groups. Dan-gua Fang could effectively improve the pathological changes in liver of diabetic ApoE-/-mice in DGF group than in D+T and TZD groups, such as ectopic fat deposition, inflammation and fibrosis.Conclusion:Dan-gua Fang had better effect on improving glucose and lipid metabolism. Dan-gua Fang could decreased four liver fibrosis indicators, improved the clinical symptoms and overall efficiency of clinical treatment in type2diabetes patients, Dan-gua Fang could moderately control food intakes and body weight, reducing ectopic fat deposition, degeneration, inflammation and fibrosis in liver in experimental animals. Those effect, in addition to closely related with the method of stasis-dissipating and phlegm-removing, part of the mechanism maybe correlated with improvement of the signal transduction pathway expression of SIRT1-LKB1-AMPK and AdipoR2inliver, concentration of APN and pACC in blood, and decrease of the expression of OB-Rb in liver. Dan-gua Fang would be an ideal drug for comprehensive intervention to glucose and lipid metabolism disorder in T2DM. |
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