Protective Effects Of Resveratrol Preconditioning On Ischemia-reperfusion Injury Of Isolated Heart In Rats

Part I Protective effects of resveratrol preconditioning on ischemia-reperfusion injury of isolated heart in ratsObjective: To study the protective effects of resveratrol preconditioning on ischemia-reperfusion injury of isolated heart in rats and its mechanism. Methods: Fifty-six male Sprague-Dawley rats were randomly divided into 4 groups with 14 animals each group: group IRI ; group resveratrol ; group L-NAME ; group AG. In the Langendorff's perfused rat hearts, the myocardial ischemia reperfusion injury was induced by the 120-min reperfusion following the 30-min ischemia. Myocardial function, myocardial NOS isoenzyme(iNOS) activity, the contents of myocardial NO and MDA were measured at the 120th minute of reperfusion.Coronary effluent was collected at 30 min of reperfusion for determination of LDH and CPK levels. Myocardial infarct size examination and electron microscopic examination.were also applied. Results: In resveratrol group LVDP and±dp/dtmax recovered significantly better than group IRI(P<0.05 or 0.01).The myocardial NO level and myocardial iNOS activity in resveratrol group were significantly higher than group IR(IP< 0.01). In resveratrol group LDH and CPK levels, myocardial MDA content, myocardial infarct size were significantly lower as compared with group IRI( P< 0.01). In L-NAME group and AG. group LVDP and±dp/dtmax recovered significantly were worse than group resveratro(lP<0.05 or 0.01). The myocardial NO level and myocardial iNOS activity in L-NAME group and AG group group were significantly lower than group resveratrol(P< 0.01). In L-NAME group and AG group LDH and CPK levels, myocardial MDA content and myocardial infarct size were significantly higher as compared with group resveratrol(P< 0.01). Myocardial injury in resveratrol group was the least among the four groups.Conclusions: Resveratrol can pharmacologically precondition the heart in a NO-dependent manner. The myocardial protection mechanism of resveratrol may be attributed to its effect on the induction of iNOS. Part II Effects of Resveratrol on myocardial apoptosis induced by ischemia-reperfusion injury in rats and its mechanismObjective: To study the effects of Resveratrol on apoptosis induced by ischemia-reperfusion injury in rats and its mechanism.Methods: Twenty-four male Sprague-Dawley rats weighing 275-300 g were anesthetized and heparinized. The hearts were rapidly removed after thoracotomy and mounted on a Langendorff apparatus via ascending aorta and perfused with oxygenated (95%O2-5%CO2) modified Krebs-Henseleit bicarbonate buffer(KHB) at 100 cm H2O (perfusion pressure) and 37℃。The animals were randomly divided into 3 groups: group IRI ; group resveratrol; group L-NAME. Global myocardial ischemia was induced by suspension of perfusion for 30 min followed by 120 min reperfusion. At the end of reperfusion, the concentrations of nitric oxide and the activities of nitric oxide synthase(NOS) were examined.The myocardial cell apoptosis was determined with terminal deoxynucleotidyl trnasferase-mediated dUTP-fluoresce in nick end labeling(TUNEL) method.Bcl-2/Bax protein expression were detected by immunohistochemical and image analysis.Results: Compared with IRI group and L-NAME group, resveratrol group obviously decreases myocardial apoptosis and markedly increased the activity of NOS, the content of nitric oxide, increased the protein expression of Bcl-2 gene, the ratio of Bax to Bcl-2 was decent incidentally.Conclusions: Resveratrol could obviously decreases myocardial apoptosis induced by IRI. The mechanisms may be associated with enchancing the activity of NOS, increasing the content of NO and upregulating the protein expression of Bcl-2 gene.