Study On The Relationship Between Diabetic Cardiomyopathy And Apoptosis/apoptosis Related Factors (Fas, Bcl-2)

Objective and background: People suffered from diabetes mellitus (DM) are increasing with the increase of economy and our living standard level. Type 2 diabetes mellitus (T2DM) is the major form (95%) of DM, and it is characterized by hyperglycemia resulted from combination of insulin resistance and alteration of -cell function. Cardiovascular complication is the leading cause of morbidity and mortality in type 2 DM. Abnormal ventricular systole and diastole are reported in both type 1 and type 2 diabetes patients presenting without macrovascular disease or hypertension, which provides indirect evidence that there is diabetic cardiomyopathy in human [1,2]. Furthermore, in clinical studies, detectable cardiac dysfunction has been reported to occur as early as the glucose intolerance phase [3] More direct evidence of diabetic cardiomyopathy has come from various animal models of diabetes [4~6]. The cellular mechanisms of diabetic cardiomyopathy in models of type 1 DM are well characterized, but little is known about the pathogenesis of cardiomyopathy in type 2 DM [7,8]. Type 2 DM is clinically more prevalent than type 1, but understanding the pathogenesis of cardiomyopathy is complicated by numerous comorbidities in both humans and animal (e.g., hypertension, obesity, hyperinsulinemia, hyperglycemia, and dyslipidemia). Studies into the etiology of this myopathy have been hampered by the lack of an adequate animal model. Most studies have been carried out using models that more closely resemble type 1 DM; these animals are overtly hyperglycemia andcontinue to waste throughout their lifetime. Wier GC. et al[9] described a chemically induced diabetes in the rat that appears resemble human T2DM. Schaffer SW et al[10] reported the development of a cardiomyopathy in rats made glucose intolerant by this method that resembles the cardiomyopathy, which occurs in human T2DM. We observed the influence of hyperglycemia to the cardiomyocytes from impaired glucose tolerance (IGT) to clinical DM (cDM) posed on the animal models of T2 DM resemble theirs [9,10l Methods(1) The neoborn male Wistar rats were divided into two groups: diabetic groups (group , n=10 5) and controlled (groups , n=5 X 5). The diabetes were injected STZ, 90mg/kg within two days after their born. Control little rats received sham injections of citrate buffer.(2) The tolerance of glucose was detected in the 8th week of diabetic group 10th week of the next four groups for determination of the animal models of T2DM.(3) Tissue from the left ventricular was observed under the electron microscope.(4) The expression of bc1-2 and fas proteins in myocytes was examined by immunocytochemical stain.(5) Programmed cell death was assessed by the terminal dexynucleotidyl transferase assay and by the electron microscope.All above programs were the same for the control groups. Results(1) The diabetic rats weighed (g) lighter than the control groups: (142.60 31.76vs203.60 13.11) at 8 weeks and (234.10 + 31.67 vs 345.20 + 39.21) at the end of the study.(2) The fast blood glucose (BG, mmol/L) increased slightly in the diabetes (7.76 + 0.85 vs 5.34?0.82) , while it was with much higher BG after dinner compared to the controlled (9.93 1.75 vs 5.63 0.79) at 10 weeks.(3) The cardiomyocytes were denaturalized: the fibre was metamorphic and arranged mussily while the mitochondria swelled and hyperplasia locally where the fibre denaturalized.(4) The expression of bcl-2(positive cells/500 100%) in myocytes was almost the same between 8 week and 16 week of the diabetic rats (1.54+0. 85% vs 1. 22?0. 57%) ; while fas (positive cells/500 100%) increased from 2.26 + 1.70% to 20.78 + 5.57% during our experiment.(5) Finally, myocyte cell death by apoptosis (positive cells/per section) comprised 1. 90 1. 60 on 8 weeks and increased to 10. 90 + 6. 81 when it came to 16 weeks.Conclusion The Wistar model was appropriate for T2DM and diabetic cardiomyopathy (DCM).