Effects of phytoestrogen genistein on myocardial ischemia／reperfusion injury and apoptosis in rabbits

INTRODUCTION Ischemia/reperfusion (I/R) injury is often seen inclinics which pathogenesis has not been elucidatedclearly. It is generally believed that its mechanism isrelated to lipid peroxide induced by oxygen free radi-cals and to irreversible damage caused by intracellularcalcium overload. The Ca2 overload is induced mainlyby the action of sarcolemmal Na /H and Na /Ca2 ex-changers1,2], which then activates several intracellularprocess, resulting in myocyte death3-5]. Genistein…

Effects of phytoestrogen genistein on myocardial ischemia/reperfusion injury and apoptosis in rabbits

AIM: To study the effect of genistein (GST) on rabbit heart ischemia/reperfusion (I/R) injury. METHODS: Rabbit heart I/R injury was induced by occluding the left anterior descending coronary artery for 45 min and reperfusing for 180 min. GST (1.0 mg/kg) was intravenously injected 5 min before heart ischemia. Hemodynamic data, infarct size, and cardiomyocytic apoptosis were measured. The pathologic changes of I/R myocardium were observed. RESULTS: During the I/R, heart rate, mean arterial blood pressure, myocardial oxygen consumption, left ventricular (LV) -dp/dtmax and +dp/dtmax were decreased progressively. The infarct size was occupied 60.23 %+/-3.97 % (% of area at risk) in vehicle +I/R group while GST reduced the infarct size to 39.62 %+/-4.30 % (P<0.01). DNA ladder pattern in myocardium was revealed by agarose gel electrophoresis in vehicle +I/R group while was not found in GST+I/R group. Apoptotic cardiomyocytes were sparse within ischemic myocardium at risk in GST+I/R group as compared with that in vehicle +I/R group (TUNEL stain). Apoptosis rate in ischemic myocardium from vehicle +I/R and GST+I/R groups detected by flow cytometry were 15.33 %+/-1.31 % and 3.88 %+/-0.33 %, respectively. Fas and Bax protein expressions in ischemic myocardium of vehicle +I/R group were higher than that in GST+I/R group (P<0.01). Bcl-2/Bax ratio in vehicle +I/R group was lower than that in nonischemic myocardium (P<0.01), while in GST+I/R group, the Bcl-2/Bax ratio was higher than that in vehicle +I/R group (P<0.01). CONCLUSION: GST reduced infarct size and apoptosis of myocytes in I/R rabbit heart.