Effect Of Metformin On Myocardial Fibrosis In Type 2 Diabetic Rats

ObjectiveThe present observe the influence of metformin on the myocardial collagen contents and the expression of transforming growth factor-β1(TGF-β1),platelet-reactive protein-1(TSP-1) in myocardial of type 2 diabetic rats,in order to explore the effect of metformin on preventing the development of myocardial fibrosis and possible mechanism .MethodsSelect 29 male SD rats, weighted 200±20g and label them with number according to their weight. Select 8 rats to constitute the normal control group(NC group) randomly and the rest 21 rats constitute the diabetes model group. Feet them with high-fat diet for four weeks and give them intraperitoneal injection frequently with low-dose of streptozotocin(30mg/kg)to produce diabetes rat molel.In the last injecton after fasting for 72 hour, caudal vein blood collection and check the blood glucose level, and recognise the diabetes model according to the blood glucose level. 19 rats are produced model successfully, the model rats are divided into diabetes group(DM group) with 9 rats which are given 0.9 % saline, metformin group(MET group) with 10 rats which are given metformin tablets( ig,500mg/(kg.d)). All the rats in different groups were given medicine treatment once daily for 6 weeks respectively . At the end of the experiment, the weight of the rat was weighed; the blood glucose was measured by blood-glucose meter,all the rats are given anesthesia with 0.3 % sodium pentobarbital and collected abdominal aorta blood. the total cholesterol, triglyceride, high density lipoprotein and low density lipoprotein cholesterin was determined by Colorimetric enzyme; hemoglobin-Alc levels was determined by Glycosylated hemoglobin analyzer;in each group, insulin levels in blood plasm was determined by radioimmunoas-say(RIA) method; heart weight and the ratio of heart body weight (HW / BW) were measured;the changes of myocardial tissue was observed under optical microscopy stained by HE; myocardial collagen content was quantified through Masson-staining and expressions of TGF-β1 and TSP-1 were detected by immunohistochemical staining.The database was established with Excel 2003, the analysis was carried on with SPSS16.0, and the results were indicated as x±s, used One-Way ANOVA, with P <0.05 as significant difference standards.Results1.Lipids: The level of TG,TC,and LDL were significantly higher in DM group rats(P<0.05),metformin therapy could reduce the TG,TC,and LDL(P<0.05);The level of HDL was significantly lower in DM group rats(P<0.05),metformin therapy could increase HDL(P<0.05).2.Hemoglobin-Alc: The level of HbAlc was significantly higher in DM group rats (P<0.05),metformin therapy could reduce the HbAlc(P<0.05).3.FBG and insulin resistance:The level of FBG and HOMA-IR were significantly higher in DM group rats(P<0.05),metformin therapy could reduce the FBG and HOMA-IR(P<0.05).4.HW/ BW ratio: Compared with NC group,DM group rats displayed more lower body weight and higher HW/ BW ratio (P<0.05), metformin could reduce the HW/ BW ratio (P<0.05).5.HE results: In NC group rats myocardial cells are well-arranged ,have normal shapes and no hypertrophy,nuclei were obvious present round or oval,cell is not swelling, has less extracellular matrix and small quantity of fibroblasts;In DM group rats myocardial cells'arrangement are disordered, cardiac muscle hypertrophy,distorted,the cell gap increases, extracellular matrix and fibroblasts growes,and inflammatory cells infiltration; In MET group rats cardiac pathology is improved,muscle hypertrophy is rare,cell borders is clear,nuclei is round or oval. 6.masson staining:Compared with NC group , the myocardial collagen contents were significantly increased in DM group and MET group (P<0.05);Compared with DM group , the myocardial collagen contents were significantly reduced in MET group.7.Immunohistochemistry results:Compared with NC group , the expressions of TGF-β1 and TSP-1 were markedly increased in DM group and MET group (P<0.05);Compared with DM group , the expressions of TGF-β1 and TSP-1 were significantly reduced in MET group.Conclusions1. Metformin could reduce the myocardial collagen contents,reduce the production of the myocardial fibrosis in type 2 diabetic rats,2. 2. Metformin could reduce the expressions of TGF-β1 and TSP-1 in cardiac tissue of type 2 diabetic rats.