| Objective: Diabetes mellitus is a clinic syndrome which is related to the interaction of heredity and environment factors. With the increasing incidence and developing course of the disease the inception rate of diabetic cardiovascular disease, it is one of diabetic complications and becomes one of the major dead factors in diabetic patients, is more and more. Diabetic cardiomyopathy is an independent diabetic complication which is a specific cardiac disease of diabetes mellitus. The effects of advanced glycation end products (AGEs) and its receptors (RAGE) produced within the environment of hyperglycemia by diabetes mellitus have been attracted more and more attentions. The interaction of AGEs and RAGE can inducing many oxygen free radicals and cytokines, such as blood vessel damage,hemodynamics and hemorrheology endothelium abnormality,cellmatrix paraplasmand neovascularization.There is a close relationship between oxidative stress and diabetic cardiovascular disease,too. The oxidative stress occurs as a result of an imbalance between the production of reactive oxygen species (ROS) and the antioxidant defence mechanisms present in biological systems.The increased ROS can activate many transcription factors,such as NF-kappa B,thus induce inflammation and augmentthetranscription of protein gene relating cell proliferation and adherent. In this study the expression of RAGE and the contents of the antioxygen SOD,GPX and peroxidation product MDA are detected in SD rats cardiac muscle in order to approach pathogenesyand afford new inspiration and pathway to clinicaltreatment.Method:1.The object :Fifty adult male SD rats weighted 180~200gram, divided into four groups randomly:4 week- control group(N4),4 week-diabedic group(D4),8week- control group(N8),8 week-diabedic group(D8).The diabetic groups were madediabetic by a single injection of streptozotocin at a dose of 60mg/kg body weight.The control groups were given citrate with the same dose.Two rats is reject and four rats died because of infection or ketosis during the period .2. The specific method: (1)The SD rats were weighted and taken blood capillaryto determine the level of glucoce,HbA1c when they were 4 weeks and 8 weeks after maken diabetic. Then took the heart out of them and weighted,then every heart was divided three parts :one part(left ventricle) which is about 0.5×0.5 kilometer is taken into 4% formalin applying HE staining methods to observe the morphologic changes in myocardium,the other parts which weighted dependently about 200 mg and 100 mg (left ventricle) ; were taken into luid nitrogen,then stored at -20℃,-80℃,applying biochemistry and RT-PCR determin.(2) The morphology observation were performed by using routine histology method HE sraining. (3) The gene expression of RAGE in the heart were mesured by RT-PCR .(4) To take the heart to measure the levels of free radical scavengers GSH-PX,SOD and the major medium production of lipid peroxidationMDA.Results: 1.Compared with N4,N8 rats differently,glucose and HbA1c of the D4,D8 rats were all significantly increased (p﹤0.01),the weight of them were all significantly increased (P<0.01), the ralative weight of heart were increased.(p P<0.01).2.Compared with normal rats, there was no pathological changes of myocardium in 4-week-DM rats, but in 8-week-DM rats, the changes were obviously: the swollen cardiac muscle cells,the pyknotic nucleoli,the hyperchromatic nucleus and the hyalinedsmallarteries. 3. Compared with normal rats,the activition of GSH-Px in D4,D8 were decreased(p﹤0.01), SOD was decreased(p﹤0.01), but MDA was increased(p﹤0.01); Compared with D4,the activition of GSH-Px,SOD in D8 were decreased (p﹤0.05), MDA was increased(p﹤0.05). 4.Compared with normal rats, the level of gene RAGE in D4,D8 was siginificantly increased (p﹤0.01). Vs D4 group, the level of gene RAGE in D8 was siginificantly increased(p﹤0.05).Conclution:1.the cardiac muscle of 8-week diabetic rat is damaged,and the changes were obviously: the swollen cardiac muscle cells,the pyknotic nucleoli,the hyperchromatic nucleus and the hyalined small arteries. 2.On diabetic rats,the activity of antioxygen material was decreased,but oxidative product was significantly increased ,indicating that the capability of antioxygen in the heart of diabetic rats was attenuated and the oxidative stress was enhanced,and change obviosly with the disease course. .3. Compared with nondiabetic rats,the contents of RAGE in the heart of diabetic was siginificantly increased,indicating that RAGE was possible participate in diabetic cardiomyopathy.4. RAGE and oxidative stress were possiblly both take part in the development and proggression of diabetic cardiomyopathy,furthermore RAGE may enhanced the effect of oxidative stress.
|
PDF Full Text Request