Cardiac myocyte apoptosis in diabetic rats and effect of non-enzymatic glycosylation inhibitor

Lijuan FU; Dongbo PANG; Zhimin QI; Hongxin WANG

ABSTRACT

BACKGROUND:

Oxygen-derived free radicals are produced during non-enzymatic glycosylation of diabetic protein and accompanied with decrease in nitrogen monoxide (NO) synthesis so as to cause the calcium increase in cell,evacuation of pykno-granule and apoptosis induced by activating endoenzyme.

OBJECTIVE:

To observe the effects of non-enzymatic glycosylation inhibitor-aminoguanidine on apoptosis of cardiac myocyte and cardiac function in diabetic rats.

DESIGN:

Completely randomized grouping design and controlled study.

SETTING:

Pharmacological Department of Jinzhou Medical College.MATERIALS The experiment was completed at the Central Laboratory of Jinzhou Medical College between September 2002 and March 2003. Totally 54 male SD rats with 2-month old were selected.

METHODS:

Totally 36 rats were selected to establish diabetic model 60 mg/kg of streptozotocin were injected into the caudal vein. If blood glucose of rats was more than 16.7 mmol/L, the establishment of diabetic model was successful. Model rats were divided into diabetes group and aminoguanidine (AG) group with 18 in each group. Rats in each group were also divided into two 12-week groups with 8 and 12 respectively. Another 18 rats were determined as the control group at 2 time points 12 weeks (n=8) and 24 weeks (n=10). Rats in each group were fed for 12 and 24in other two groups. Calculation of mass index was [heart (mg)/body mass (g)]. Myocardial tissue of left ventricle was taken out and observed with transmission electron microscope and then stained with in situ end-labeling (ISEL) method. Number of positive nucleus was counted with 10 × 10 ocular lens check system and with 10 fields ISEL method; meanwhile, their average was obtained.MAIN OUTCOME

MEASURES:

Whether there was apoptosis of cardiac cell and the effect on AG in changes of cardiac structure and function of diabetic rats or not.

RESULTS:

Eight rats were lost during the experiment because of death mass That of rats in the 12-week and 24-week diabetic group was higher decrease and increase rate of pressure in left ventricle That of rats in the 12-week and 24-week diabetic group was lower than that in the control in left ventricle That in 24-week diabetes group was obviously lower than diabetic group was obviously more than that in AG group (P ＜ 0.01), and that in 24-week diabetes group was obviously more than that in 12-week Apoptosis could be observed in myocardial cell in diabetic group.

CONCLUSION:

Apoptosis of myocardial cell plays an important role in the development of heart failure in diabetic rats. AG can reduce the apoptosis of myocardial cell and decrease the myocardial pathomorphological abnormality.