| Objective: Diabetic cardiomyopathy (DCM) is a special chronic complication of diabetes mellitus (DM). It has a close relation with the high rate of heart failure and death in DM patients. A good many of studies showed that some major pathological hallmarks of DCM were myocardial hypertrophy, focal necrosis, myocardium mesenchyme remodeling, myocardial fibrosis and so on. Adiponectin is considered as the closest cytokine with insulin resist, which is secreted by fatty tissue. Adiponectin is connected with its receptors, exactly plays the corresponding role. However, it needs something to be done about its function during the occurrence and development of cardiomyopathy in DM. Rosiglitazone is one of thiazolidinediones which are insulin sensitizers and also has protective effects on cardiomyopathy. In this study type 2 diabetes mellitus (T2DM) rat model was copied by giving Sprague-Dawlay (SD) rats high-sugar-fat diet and a low dose of streptozotocin (STZ). Then the serum adiponectin and the protein expression of the adiponectin receptor 1 (AdipoR1) in myocardial tissue of experimental animals were detected in order to discuss the association among serum adiponectin, the protein expression of AdipoR1 and cardiomyopathy in DM. Furthermore, rosiglitazone were given to experimental rats to explain its mechanism of protective effects on myocardium.Methods: 10 of 40 SD rats were taken out randomly to be normal control rats (group A) and the rest were taken for test rats. The control rats were fed with general diet while the test rats were fed with high-sugar-fat diet (mixed 2.5% cholesterin,20% suger, 15% cooked lard and general diet together). Four weeks later, insulin resistance was induced in test group, then STZ 30 mg/kg was injected into abdominal cavity to destroy pancreas. At the end of 6 weeks, the rats whose fasting blood glucose (FBG) was higher than 7.8 mmol/L and insulin sensitivity decreased were considered as T2DM rats. T2DM rats were divided randomly into 2 groups: T2DM model rats (group B), T2DM model rats treated with rosiglitazone (group C). The experiment lasted 18 weeks. At the end of 4 and 6 weeks, body weight, FBG, fasting insulin (FINS), insulin sensitivity index (ISI), serum triglyceride (TG) and total cholesterol (TC) levels in different group rats were measured. At the end of this experiment, FBG and FINS, ISI, TG, TC, high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), very low density lipoprotein cholesterol (VLDL-C) were detected. Myocardium microstructure and ultrastructure of left ventricle were observed with light and electron microscopes. Serum adiponectin was measured by enzyme linked immunosorbent assay (ELISA). The protein expression of AdipoR1 in myocardium was detected by immunohistochemical staining. The results were analyzed with computer image-analysis system and the integral optical density (IOD) of AdipoR1 was calculated. The data were dealt with SPSS11.0.Results1 Various indexes after 4 weeks: Been fed with high-sugar-fat diet for 4 weeks, test rats were heavier than normal control rats (P<0.05). FBG(6.33±0.65)mmol/L, FINS 30.19(29.05, 31.65)mIU/L, TG and TC of test rats were higher than FBG(5.13±0.46)mmol/L, FINS 19.45(17.99, 20.99)mIU/L , TG and TC of control rats (all P<0.01). At the same time, ISI 0.0053(0.0050, 0.0054) in test rats was lower than ISI 0.0101(0.0100, 0.0102) in control rats (P<0.01).2 Various indexes after 6 weeks: 2 weeks after STZ injection, FINS 18.79(18.23, 19.29)mIU/L in test rats compared to FINS 18.35(17.95, 18.98)mIU/L in control rats was unstatistics distinction (P>0.05). Other features were retained. FBG(13.18±1.47)mmol/L in test rats was higher and ISI 0.0048(0.0045, 0.0053) was lower than FBG(5.04±0.46)mmol/L and ISI 0.0106(0.0103, 0.0112) in control rats (both P<0.01). Thus far, the T2DM rat model was accomplished.3 Various biochemical indexes after 18 weeks: When the experiment was finished, There were FBG(4.89±0.35)mmol/L, FINS17.66(16.83, 18.27)mIU/L and ISI 0.0111 (0.0104, 0.0121) in group A rats, FBG(12.43±1.48)mmol/L , FINS 20.95(19.81, 22.11)mIU/L, TG, TC, LDL-C and VLDL-C in group B rats were all higher than those in group A rats. HDL-C and ISI 0.0039(0.0036, 0.0041) in group B rats were lower than those in group A rats (all P<0.05). FBG(9.01±1.14)mmol/L and FINS 18.45(17.97, 18.76) mIU/L and foregoing items in group C rats were lower than those in group B rats. HDL-C and ISI 0.0065(0.0057, 0.0069) in group C rats were higher than those in group B rats (all P<0.05).4 Serum adiponectin: At the end of 18weeks, serum adiponectin (1.01±0.27)μg/mL in group B rats was lower than that (1.73±0.32)μg/mL in group A rats (P<0.05). And foregoing item (1.34±0.43)μg/mL in group C rats was higher than that in group B rats (P<0.01). Related analysis showed that serum adiponectin level had a negative correlation with FBG, FINS and LDL-C (r=-0.656, -0.359 and -0.637, all P<0.01), a positive correlation with HDL-C and ISI (r=0.614 and 0.615, both P<0.01) in experimental rats.5 The protein expression of AdipoR1 in myocardium: The IOD (34.45±9.97) of AdipoR1 in group B rats was 52% of that (66.42±7.1) in group A rats (P<0.01). And the IOD (49.32±16.28) in group C rats was 1.43 times of that in group B rats (P<0.01). Related analysis showed that myocardial AdipoR1 expression had a negative correlation with FBG and LDL-C (r=-0.665 and -0.702, both P<0.01), a positive correlation with HDL-C and ISI (r=0.733 and 0.684, both P<0.01) in experimental rats.6 Morphology: HE staining showed that cardiac fiber of group A rats were in order, cross striation was clear, karyon and intercellular space was normal. While in T2DM model rats, cardic muscle degeneration, focal necrosis and region adipocytes infiltrating could be observed. Foregoing changes in group B rats were more severe than those in group C rats. The myocardial ultrastructure of group A rats appeared that myofibril was in order, light and dark band was clear and the configuration of mitochondrion was normal. Group B rats had some pathological characteristics of myofibril disorder, mitochondrion edema, endoplasmic reticulum dilatation, CL hyperplasia, hepatin and lipofuscin deposition, capillary basement membrane incrassation, etc. Foregoing changes in group C rats were more relieve than those in group B rats.Conclusions1 The type 2 diabetic rat model that was induced by high -sugar-fat diet and a low dose of STZ had some characteristics similar to human T2DM. It would be available to study T2DM and its complications.2 Serum adiponectin and the protein expression of AdipoR1 in myocardium of T2DM rats were decreased. It indicated that adiponectin and AdipoR1 was closed to the occurrence and development of DCM.3 Related analysis showed that the serum adiponectin and AdipoR1 protein expression in myocardial tissue had a tight association with hyperglycemia, hyperlipemia and insulin sensitivity. It illuminated that the study on adiponectin and AdipoR1 might afford new theory to prevent and treat DCM.4 Rosiglitazone could relieve myocardial lesion of T2DM. It might be due to their beneficial effects on general metabolism and increasing in serum adiponectin and the protein expression of AdipoR1 in myocardium of T2DM rats.5 Cardic muscle degeneration, focal necrosis, region adipocytes infiltrating, and mitochondrion edema, cristae collapse coalesce were principal pathologic foundations of cardiomyopathy in T2DM.
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