| Objective:Type 2 diabetic rats were induced by feeding with high-fat and high-sugar diet and then injecting a low dose of streptozotocin (STZ) by abdominal cavity. To investigate the effects of telmisartan on the expression of AdipoR2 and GluT4 in the heart of type 2 diabetes rats.To observe the preventive and therapeutic effects of telmisartan on diabetic cardiomyopathy.Methods:Ten of Thirty-six male Wistar rats were randomly taken out to be normal control group (group A, n=10) and the rest were made for type 2 diabetic(n=26). The rats in group A were fed with standard diet while the diabetic rats were fed with high-sugar and high-fat diet. Four weeks later, the diabetic rats were injected with a low dose of STZ(30mg/kg) by abdominal cavity. At the end of six weeks,the rats with fasting blood glucose (FBG)≥7.8mmol/l and insulin resistance were considered as type 2 diabetic models. Twenty diabetic rats were randomly divided into 2 groups: diabetic control (group B, n=10)and diabetic treated with telmisartan (group C, n=10). Group C was administrated with telmisartan (5mg/kg/d) by lavage. Group A and B were administrated with equivalent volume of normal sodium by lavage. After 12 weeks, all animals were fasted for 12h,then the body weight was measured. After the rats were anesthetized, the heart function was measured. The rats were sacrificed after blood was obtained by abdominal cardinal vein. The blood preparation was used to measure plasma glucose,insulin,triglyceride,cholesterol and adiponectin levels,the insulin sensitivity was calculated. The heart was immediately taken out of thoracic cavity after the rat was sacrificed. The heart was rinsed with normal sodium and dried by filter-paper and then weighed. The part of cardiac ventricle was immediately thrown into the liquid nitrogen and then stored in the-70℃refrigerator, The rest part of cardiac ventricle was fixed by formalin and then was dehydrated, imbedded by paraffin and sliced for immunohistochemistry stain. The levels of myocardial AdipoR2,GluT4 and MCP-1mRNA were measured by RT—PCR. The protein expression of myocardial AdipoR2 was detected by immunohistochemical staining. Plasma adiponectin levels were measured by enzyme linked immunosorbent assay (ELISA).Results:1. Compared with group A, untreated diabetic rats (group B) showed higher ratio of heart to body weight.The levels of fasting blood glucose,plasma insulin, triglyceride and cholesterol were significantly increased in group B than those in group A(P<0.05). The insulin sensitivity index was significantly reduced in group B than that in group A (P<0.05). After telmisartan treatment, group C showed lowered ratio of heart to body weight,fasting blood glucose, plasma insulin, triglyceride and cholesterol compared to group B. The insulin sensitivity index was significantly increased in group C than that in group B (P<0.05).2. Plasma adiponectin level and the expression of myocardial AdipoR2. Compared with group A, plasma adiponectin level, the protein and mRNA expression of myocardial AdipoR2 were significantly decreased in diabetic rats (groupB) (P<0.05). After treatment with telmisartan, plasma adiponectin level, the protein and mRNA expression of myocardial AdipoR2 were significantly increased in diabetic rats (group C) (P<0.05).3. The mRNA expression of myocardial GluT4. Compared with group A, the mRNA expression of myocardial GluT4 was significantly decreased in groupB (P< 0.01). After treatment with telmisartan, the mRNA expression of myocardial GluT4 was significantly increased in group C(P<0.05).4. The mRNA expression of myocardial MCP-1. Compared with group A, the mRNA expression of myocardial MCP-1 was significantly increased in groupB (P< 0.05). After treatment with telmisartan, the mRNA expression of myocardial MCP-1 was significantly decreased in group C(P<0.05).5. The results of the myocardium stained by MASSON:Observed through the light microscope: The myocardial cells lined up in order, the size of cellular nucleus was the same,it was spherical or ellipse, and it was stained in uniformity in group A. Group B rats:the myocardial cells lined up in disorder, the size of cellular nucleus was irregular. There were fibrocyte proliferation in the cardiac muscle fibers and extent of cell was obfuscation, the collagen fibers accrescence between myocardial cell. Group C rats were outweigh to Group B rats, cell degeneration had improved.6. Heart function. Compared with group A the maximum descent-speed of pressure in the left ventricle isovolumic relaxation period(-dp/dtmax) (mmHg/s) was significantly decreased in group B(P<0.05). After telmisartan treatment, the (-dp/dtmax) was obviously higher in groupC than group B (P<0.05).Conclusion 1. The model of type2 diabetic rats was successfully induced.lt would be available to study T2DM and its complications.2. The ratio of heart to body weight was significantly increased, plasma adiponectin level, the protein and mRNA expression of myocardial AdipoR2, and the mRNA expression of myocardial GluT4 were significantly decreased in diabetic rats (group B). After treatment with telmisartan, the ratio of heart to body weight was significantly decreased, plasma adiponectin level, the protein and mRNA expression of myocardial AdipoR2, and the mRNA expression of myocardial GluT4 were significantly increased in diabetic rats (group C).3. The mRNA expression of myocardial MCP-1 was significantly increased in diabetic rats (group B). After treatment with telmisartan, the mRNA expression of myocardial MCP-1 was significantly decreased in diabetic rats (group C).4. Telmisartan up-regulates the expression of myocardial AdipoR2 and GluT4,reduce the expression of MCP-1 in the myocardium of diabetic rats, promotes myocardial glucose oxidation, reduces cardiac hypertrophy and thus produces heart protection in diabetic rats.
|
PDF Full Text Request