Study On The Relationship Between Myocardial Chymase And Diabetic Cardiomyopathy

Diabetes mellitus is one of the most prevalent chronic conditions threatening public health. Cardiovascular complications are the major causes of death, among which diabetic cardiomyopathy is associated with the high morbidity and mortality of heart failure. Understanding the mechanism of diabetic cardiomyopathy and providing effective treatment are of theoretical value and clinical significance. The development of diabetic cardiomyopathy is due to the interaction of multiple factors, including disturbance of metabolism, disorder of microcirculation, peroxidation, disability of autonomic nerve, growth factors, neuroendocrine factors and so on. It has been found recently that activation of angiotensin Ⅱ(AngⅡ) plays an important role in the development of diabetic cardiomyopathy. It is believed that AngⅡ in the hearts can be produced not only by classical angiotensin- converting enzyme (ACE) pathway, but also by chymase pathway. Chymase is a chymotrypsin-like serine protease. Human and hamster chymases cleave angiotensin Ⅰ(AngⅠ)to yield AngⅡ. It was found that chymase was activited in many kinds of heart disease. And chymase was activated in diabetic nephropathy patients. Thus it is supposed that chymase may be a mediator of diabetic cardiomyopathy.Both angiotensin-converting enzyme inhibitor (ACEI) and angiotensin Ⅱ AT1 receptor blockers (ARB) inhibit the activity of the rennin-angiotensin system (RAS), but these two classes medications have different mechanisms of action. More and more clinical trials demonstrate that ACEI and ARB have beneficial effect on many kinds of heart diseases. In the present study, we measured mRNA expression and activity of chymase and ACE in diabetic cardiomyopathy hamsters, tested the influence of ACEI and ARB on mRNA expression and activity of chymase and ACE, observed the therapeutic effect of ACEI and ARB on diabetic cardiomyopathy, so as to test the hypothesis that chymase is associated with diabetic cardiomyopathy and investigate the possible therapeutic mechanism of ACEI and ARB. It will provide theoretical basis for doctors' choosing drugs and for producing new kinds of medications. Part Ⅰ Establishment of Diabetic Hamsters and the Characteristic of Diabetic CardiomyopathyObjective: Diabetic cardiomyopathy hamsters were induced by injecting streptozotocin (STZ) intraperitoneally. This model is used to investigate the role of chymase in the development of diabetic cardiomyopathy.Methods: ①STZ was used to establish diabetic hamsters. And normal hamsters were tested as controls. Body weight and blood glucose were measured every 2 weeks. Research work lasted 10 weeks. ②Heart rate and blood pressure were measured by introduction of catheter into carotid artery. ③Insulin, C-peptide, lipoprotein (triglycerides TG, cholesterol CHO, low density lipoprotein LDL and high density lipoprotein HDL), myocardial enzymes (aspartate aminotransferase AST, creatine phosphokinase CPK and its isoenzyme CMB, lactate dehydrogenase LDH) and glycosylated serum protein (GSP) were tested. ④Myocardial tissues were observed by HE and Van-Gieson (V-G) stain. Myocardial ultrastructure was observed by electric microscopy. Results: ①Compared with normal (NC) group hamsters, body weight and heart weight in diabetic (DM) group were much lower (P(0.001). While the ratios of heart weight / body weight were comparable between the two groups. ②Levels of blood glucose in DM group were much higher that those in NC group (P(0.001). And levels of serum insulin and C-peptide in DM group were much lower (P(0.01, P(0.05). ③Compared with NC group, levels of TG, CHO and LDL in DM group were much higher, while levels of HDL were not different from those in NC group. ④Levels of AST, CPK and CMB in DM group were higher than those in NC group (P(0.01). Levels of LDH were similar in the two groups. ⑤Compared with NC group, heart rates, systolic arterial blood pressure (SBP), diastolic arterial blood pressure (DBP) and mean arterial blood pressure (MBP) in DM group were much lower. ⑥Diabet...