| With social development and change of life style, Diabette Mellitus(DM) has become one of the most important and popular disease. It is common for diabetic patients to develop congestive heart failure(CHF). CHF is the leading cause of death in diabetic patients . Framingham's study revealed that in patents over 18 years old the CHF is approximately 2.4 as frequent in male patients with diabetes compared with patients without the disease and 5.1 in female patients .Prior to 1972, the increased cardiovascular morbidity and mortality that diabetics endure had been attributed to vascular disease. Although coronary artery disease is accelerated in the diabetic state,it has been recognized for a number of years that diabetes independently impairs myocardial performance by decreasing cardiac muscle function. In 1972, Rubier et al proposed the existence of a diabetic cardiomyopathy based on their expereince with four adult diabetic patients who suffered from CHF in the absence of discernable coronary artery disease, valvular or congenital heart disease, hypertension, or alcoholism. The concept of diabetic cardiomyopathy is independent of atherosclerotic cardiovascular disease. The exact mechanism is still questionable, and several mechanisms have been proposed including small and microvascular disease, autonomic dysfunction, metabolic derangements, and interstitial fibrosis.However,the underlying mechanisms of the sequential development of cardiac contractility remain unknown. During the last decade there was accumulating evidence that alterations of excitation-contraction (EC) coulpling may play a critical role in the pathophysiology of myocardial failure. EC-coulpling comprises processes involved in calcium activation of contractile proteins and the the subsequent removal of calcium facilitating relaxation. The initialevent is depolarisation of the membrane which opens voltage-gated, dihyopropyridine-sensitive sarcolemmal L-type calcium channels allowing an influx of calcium into the myocyte. The entry of a small amount of Ca2+ produces a localized increase of Ca2+ in the small spaces between the surface and sarcoplasmic reticulum(SR) membranes.This then increases the open probability of the SR calcium release channels resulting in the efflux of Ca2+ from the SR into the cytoplasm.Then the contraction of cardiac muscle is initiated .Two different types of channels are known termed ryanodine receptor type 2 (RyR2) and inositol 1,4,5-trisphosphate receptor type 2 (IP3R2). In the cardiac SR, the density of the RyR2 is significantly higher than that of the IP3R2 -Obviously,for the heart to function as a pump,it must relax as well as contract. Relaxation is initiated by a reduction of Ca2+ produced mainly by pumping back into the SR by the SR Ca2+-ATPaes(SERCA).The SERCA is regulated by phospholamban (PLB) which is an inhibitor of the SERCA.Aim:To examine potential mechanisms underlying the development of cardiomyopathy in diabetes, we use male Sprague-Dawley rats as an animal model of diabetes that mimics the sequential development of cardiomyopathy in diabetic patients. The ultrastructure of myocardium and gene expression of calcium handling proteins including SERCA, PLB, RyR2,IP3R2 and L-type calcium channel in diabetic rat hear were investigated.Method:Male 4-wk-old Sprague-Dawley rats initially weighing 180-230g were purchased from College of Medicine Sciences, ZheJiang University and housed in the animal laboratory of Sir Run Run Shaw Hospital. Rats were made diabetic by administering a single tail-vein injection(40mg/kg ) of alloxan ,and the control group was injected with normal saline only. At the end of 2,4 and 6 weeks after the injection, the animals were killed and the blood glucose levels were tested by using reageant strips . The hearts were rapidly removed and washed in ice-cold 0.9% NaCl solution, and the atria and aorta were cut off. A littlt tissue at the apex was obtained for light and electron microscope study. The ventricles were freeze-clamped at liquid N2 temperature between a pa...
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