Effect Of Probucal On Ischemia/Reperfusion-induced Myocyte Apoptosis In New Zealand White Rabbits

Objective : To investigate the effect of probucol on ischemia/reperfusion -induced myocyte apoptosis, the total activity of serum superoxide dismuase (T-SOD), and serum concentration of malondialdehyde(MDA) in New Zealand White rabbits and its possible mechanism.Methods: Thirty male New Zealand White rabbits were randomly divided into three groups: sham, control and pretreatment. Each group involves ten animals. The rabbits were fed daily with ordinary food. The animals of treated group were additionally fed daily with probucol(l 000mg/d), Four weeks later the model of ischemia/reperfusion was established in both control and pretreatment animals. In the sham group, the heart was exposed after the chest had opened, but coronary artery wasn't ligated. One hundred and fifty minutes after the procedure, theanimals were killed. In the other two groups, the rabbits were subjected to a thirty minutes coronary occlusion followed by a two-hours reperfusion. Electrocardiogram was recorded before ischemia and postischemia respectively, and ST segment elevation means success in establishment of the model. Blood samples were extracted from right atrium before the animals were killed, and the blood was isolated with hypothermia high speed centrifugation. The serum was kept in hypothermia refrigeration(-70 ). The myocardial tissue of ischemic region was resected promptly after animal was killed, and was embedded in paraffin wax after fixed with 10% neutral formaldehyde solution and disposed with routine histological section( 4 m). The apoptotic myocytes were assessed by terminal deoxynucleotidyl transferase-mediated dUTP nick and labeling (TUNEL). Also, the total activity of serum superoxide dismuase was tested by the method of xanthine oxidase, and the content of serum malondialdehyde was checked by colorimetry.Results: The apoptotic index of myocytes in control group (34.75 3.20)% or pretreatment group (22.71 2.76)% was significantly higher than that in sham group[(0.48 0.20)%, P<0.01 for each]. The apoptotic index of myocytes in pretreatment group was significantlylower than that in control group(P<0.01). The activity of serum superoxide dismutase in pretreatment group(162.61 16.13 u/L) was higher than that in control group(144.27 21.69 u/L, P<0.05), but significantly lower than that in sham group(204.64 16.67 u/L, P<0.01). The serum concentration of malondialdehyde in pretreatment group(1.95 0.51 u mol/L) was significantly lower than that in control group(2.70 0.51 mol/L, P<0.01), but significantly higher than that in sham group(1.06 0.46 mol/L, P<0.01).Conclusion: The present study shows that probucol could reduce ischemia/reperfusion-induced myocardial injury as well as myocyte apoptosis. This effect of probucol may be due to the increases of serum superoxide dismutase activity and serum malondialdehyde concentration.