| ObjectiveTangningtongluo tablet is the hospital preparation of Guizhou Bailing Group Pharmaceutical Co.,Ltd.In the state administration of traditional Chinese medicine science and technology special support,this topic was to explore the pharmacodynamic effects and related mechanisms of Tangningtongluo tablet in delaying or reversing the development of diabetes into type 2 diabetes,to lay the foundation for Tangningtongluo tablet to apply for new Chinese medicine,and provide reference for expanding the clinical indications of Tangningtongluo tablet.MethodsEstablishment of the mice model of pre-diabetes mellitus: 120 SPF Kunming mice,20 mice were randomly selected as the control group and fed on the regular chow diet for 4 weeks;the remaining mice were given a single intraperitoneal injection of STZ 30mg/kg buffer induced the model of PDM mice after 4 weeks of feeding the high-glucose and high-fat diet.The control group was injected with equal volume of citric acid sodium citrate buffer solution.FBG and 2h PG were measured on days 7 and 14 after STZ injection,blood glucose values in the(1)(6.2 mmol/L≤FBG<7.0 mmol/L and 2h PG<7.8 mmol/L)or(2)(FBG<7.0 mmol/L and 7.8 mmol/L≤2h PG<11.0 mmol/L)range were considered PDM mice.Blood glucose values in the(FBG<6.2 mmol/L and 2h PG<7.8mmol/L)range were considered control mice.Group and administration of experimental animals: PDM mice were randomly divided into the model group,the metformin positive drug group(200mg/kg),the TNTL low(0.5 g/kg),medium(1.0 g/kg),and high(2.0 g/kg)dose groups,the control group and the PDM model were given equal volume of solvent.Mice in each group were given corresponding drugs for 28 consecutive days.Detection of animal experimental indicators:(1)General indicators: The body weight,FBG and 2h PG of all mice were tested weekly before and after administration;after the administration,all mice underwent an OGTT experiment,draw the OGTT curve diagram and calculate the AUC.(2)Detected the levels of TG,T-CHO,LDL-C,HDL-C,ALT,AST,SOD,MDA and GSH-px in serum of mice for kits.(3)The morphological changes of liver and islet tissues were observed by HE staining.(4)By ELISA detects the levels of inflammatory cytokine IL-1β and IL-6,TNF-α,and the levels of the Hb A1 c and FINS to assess HOMA-IR.(5)By WB detects the expression levels of PI3 K,p-PI3 K,AKT,p-AKT,IKK,p-IKK,NF-κB p65 and p-NF-κB p65.Results(1)TNTL tablet changes in weight and blood glucose in PDM mice:Compared with the control group,the body weight,FBG and 2h PG were higher in the model group(P<0.01);compared with the model group,body weight decreased in each dose group(P<0.01),FBG and 2h PG were decreased in each dose group(P<0.05).(2)TNTL tablet change in Hb A1 c in PDM mice: Compared with the control group,the level of Hb A1 c was increased in the model group(P<0.01);compared with the model group,the level of Hb A1 c was decreased in the medium and high-dose groups of TNTL tablet(P<0.01).(3)Relative risk reduction rate of diabetes mellitus(%): Four weeks after administration,the risk of conversion to diabetes decreased by 50% in the metformin group,the risk of PDM mice to diabetes was reduced by 25% in the low dose group of TNTL tablet,and the risk were reduced by 37.5% in the medium and high dose groups of TNTL tablet.(4)TNTL tablet changes in blood lipid profile in PDM mice: Compared with the control group,the levels of TG,T-CHO and LDL-C were increased(P<0.01)and the level of HDL-C was decreased(P<0.01)in the model group;compared with the model group,the levels of TG and T-CHO were decreased in the medium and high dose group of TNTL tablet(P<0.05),the level of LDL-C was decreased in metformin group and high dose group of TNTL tablet(P<0.05),the level of HDL-C was increased in medium and high dose groups of TNTL tablet(P<0.01).(5)TNTL tablet changes in liver function in PDM mice: Compared with the control group,the levels of ALT and AST were increased in the model group(P<0.01);compared with the model group,the level of ALT was decreased in medium and high dose groups of TNTL tablet(P<0.01),and the level of AST was decreased in the high dose group of TNTL tablet(P<0.05).(6)TNTL tablet changes in FINS and insulin resistance index in PDM mice:Compared with the control group,the levels of FINS and HOMA-IR index were increased in the model group(P<0.01);compared with the model group,the levels of FINS and HOMA-IR index were significantly decreased in metformin group,the medium and high-dose groups of TNTL tablet(P<0.05).(7)Histopathological changes in the liver and pancreatic islets: HE results showed that the TNTL tablet can reduce the fat vacuolation of liver tissue,improve the swelling of liver cell disorder;improve islet tissue morphology and disordered arrangement of islet cells and increase the number of islet cells.(8)TNTL tablet changes in oxidative stress in PDM mice: Compared with the control group,the level of MDA was increased(P<0.01)and the levels of GSH-px and SOD were decreased in the model group(P<0.01);compared with the model group,the level of SOD was increased in each dose group(P<0.01),the level of GSH-px was increased in the medium and high dose groups of TNTL tablet(P<0.01),and the level of MDA was decreased in each dose group(P<0.05).(9)TNTL tablet changes in inflammatory factors in PDM mice: Compared with the control group,the levels of TNF-α,IL-1β and IL-6 were increased in the model group(P<0.01);compared with the model group,the level of IL-1β was decreased in the medium and high-dose group of TNTL tablet(P<0.01),the levels of TNF-α and IL-6 were decreased in metformin group and the medium and high dose groups of TNTL tablet(P<0.05).(10)TNTL tablet changes in key proteins of the PI3K/AKT/NF-κB signaling pathway : Compared with the control group,the expression of p-PI3 K and pAKT were down-regulated in the model group(P<0.05),the expression of p-IKK and p-NF-κB p65 were up-regulated in the model group(P<0.01);compared with the model group,the expression of p-PI3 K was up-regulated in the medium dose group of TNTL tablet(P<0.05)and the expression of p-AKT was up-regulated in the high dose group of TNTL tablet(P<0.05),the expression of p-IKK was down-regulated in each dose groups(P<0.05),and the expression of p-NF-κB p65 was down-regulated in each dose groups(P<0.01).ConclusionsTangningtongluo tablet can regulate the disorder of glucose and lipid metabolism,improve the pathological change of liver and islet tissue,increase insulin sensitivity,improve PDM IR,eventually delay the progression of PDM to diabetes.The mechanism may be achieved by up-regulating the expression of p-PI3 K and p-AKT,increased the levels of SOD and GSH-px,decreased the level of MDA,down-regulating the expression of p-IKK and p-NF-κB p65,reduce the levels of TNF-α,IL-1β and IL-6. |
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