| BackgroudCardiovascular disease is challenging our country now in the twenty-first century,and coronary heart disease(CHD) will be "the first killer" endangering people's health in the near future.Acute myocardial infarction(AMI) is one of the common types of CHD and a critical case in emergency.Prompt intervention with AMI and obtaining myocardial reperfusion is the key procedure to secure the dying myocardium.With the development of the thrombolytic therapy,percutaneous transluminal coronary angioplasty(PTCA), coronary artery bypass grafting(CABG) and laser myocardial revascularization used in clinic ,the therapy for acute myocardial ischemia enters into the reperfusion time . Reperfusion treatment means making the occlusive cornary artery's flow restored by using thrombolytic ,balloon,stent or GABG,which has been the pivotal measure in the treatment of AMI .Meanwhile ,myocardial reperfusion injury(MRI) is attracting more and more attention of researchers and it is meaningful to prevent and cure MRI for patients of AMI treated with reperfusion therapy.It has been the important task of cardiologist to probe into the mechanism of myocardial ischemic reperfusion injury and to find the procedure to relieve or cure it.The mechanism of myocardial ischemic reperfusion injury is unclear now ,but oxidative radicals,calcium overload and activated neutral leucocytes have been accepted widely lo play a role in it. A considerable number of basal researches indicate that the reperfusion of ischemic myocardium can produce a lot of oxidative radicals and cause the vascular endotheliocytes to lose its balance ,which released more endothelial contract factors(EDCF) than endothelial relaxed factors(EDRF).]n addition, the apoptosis of myocardiocytes and the acute inflammation happening during the reperfusion also have influence on this pathological process.So with the progression of the investigation on the mechanism of myocardial ischemic reperfusion injury,antioxidative therapy as a new strategy has been developed dramaticaly.Grape seed proanthocyanidin(GSP) is a sort of polyphenols extracted from grape seeds and it has potent antioxidant activity ,capable of scavenging free radicals with low toxicity ..which suggests that GSP may have beneficial effects on the inhibition of myocardial ischemical reperfusion injury.Objective(l)To investigate the anti-MRJ effects and possible mechanisms of grape seed proanthocyanidin through the animal model of MRI .(2)To observe the effects of grape seed proanthocyanidin on the incidence of arrhythmia and the area of myocardial infarction of the hearts of rabbits induced by myocardial ischemia and reperfusion.(3)To observe the effects of grape seed proanthocyanidin on the serum crcatinc kinasc (CK), CK-MB, superoxide dismutase(SOD),malondialdehyde(MDA), nitrogen monoxide(NO), endothelins(ET) and interleukin-6(IL-6) of the experimental rabbits.(4)To observe the effects of grape seed proanthocyanidin on the apoptosis of myocardial cells of the rabbits.Methods(l)Animals and diets :24 male New Zealand rabbits were randomized into four groups with 6 rabbits in each group .They were individually housed in metal cages in an airconditioned room and were given restricted amounts of food (100-150 g/head per day ),with no limit of drinking . Observing one week before trial,rabbits of all the four groups were fed with the same amount of liquid of 2ml/kg body weight through gastric tubes every morning continuing for 21 days.Rabbits of the normal contral group and the myocardial ischemic reperfusion injury group were fed with only water;Rabbits of the high dose GSP group were fed with water containing GSP of 200mg/kg body weight and those of the low dose GSP group were fed with water containing GSP of 1 OOmg /kg body weight.(2)Samples taking :Blood samples were drawn from leg's small saphenous vein of rabbits at different times determined before research,that isjust before Jigating the coronary artery and 30 minutes after that,20 minutes after reperfusion,60 minutes after reperfusion and 120 minutes after reperfusion.Serum was obtained from the blood through centrifugal)on at 3000rpm/min for 10 minutes and then reserved in -80°C refrigeratory mensurateCK,CK-MB, SOD,MDA, NO,ET and 1L-6.A11 the rabbits were sacrificed at the end of the reperfusion of 120 minutes and the hearts of the rabbits were excised for the morphological observation and electronic microscope examination.(3)measurements :Serum CK, CK-MB was measured enzymatically by automatic facilities.Serum SOD,JvlDA, NO,ET and IL-6 were measured respectively according to the instructions of the Test Kits.Heart samples were observed through optical microscope and electron microscope seperately and stained by TUNEL method.(4)Statistical analysis :Results were expressed as meanes±SD.One~way-anova of SPSS 10.0 soft ware was used to evaluate the differences between the four groups of rabbits.ResultsCompared with the control group of ischemic reperfusion injury rabbits,(l)GSP significantly mitigated myocardia] ischemic reperfusion injury of the rabbits. (2)The effect of GSP on the vascular endotheliocyte unstabilization and the acute inflammation of the reperfusion myocardium of rabbits was not appreciable.(3)GSP has a significant effect of anti-MRJ,the mechanism of which was that it can scavenge free radicals and inhibit the oxidation of lipoproteins.(4)GSP inhibited the apoptosis of myocardium of ihe rabbits, which maybe one of the mechanisms of its anti-MRJ effect.ConclusionGrape seed proanthocyanidin had the efficacy of anti-MRJ, the mechanism of which was that it could scavenge free radicals, inhibit the oxidation of lipoproteins,and hinder the apoptosis of myocardium. |
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