The Protective Effects Of Berberine On Myocardial Ischemia-reperfusion Injury In Rats

The incidence and mortality rates of myocardial ischemic disease were yearly increasing.Clinical treatment is through a variety of ways to restore coronary blood supply to save the dying heart.But after coronary reperfusion is often accompanied by reperfusion injury.On myocardial ischemia-reperfusion injury in the mechanism and prevention,domestic and foreign has done a great deal of clinical observation and animal experiments,its mechanism has been further complement and development,and verify a large number of drugs available for prevention and treatment.Berberine as broad-spectrum antimicrobial clinical proprietary long,also found its antiarrhythmic,anti-heart failure,reduce blood sugar,blood pressure and blood lipid,anti-platelet aggregation and other extensive pharmacological effects.Berberine used in the cardiovascular system has achieved better clinical efficacy.But its mechanism has not yet been fully understood.The highest rate of cardiovascular death myocardial ischemia-reperfusion injury and its mechanism still needs further study.Objective:Observethe the protective effect and mechanism of berberine on myocardial ischemia-reperfusion injury in rats and provide the theoretical basis for the clinical application of berberine in the treatment of myocardial ischemia-reperfusion injury.Methods:Through the establishment of on isolated rat model of myocardial ischemia-reperfusion injury,to detect the hemodynamic parameters,to observe left ventricular developed pressure(LVDP),left ventricular end diastolic pressure (LVEDP),left ventricular pressure maximum rate of rise(+dp/dt) and left ventricular pressure maximum rate of descent(-dp/dt),changes on isolated detection of myocardial superoxide dismutase(SOD) activity and malondialdehyde(MDA) generation capacity.By ligating the left anterior descending coronary artery in vivo rat to establish the myocardial ischemia-reperfusion injury model,to observe the hemodynamic changes,the types and incidence of arrhythmia,myocardial infarct size, changes in vivo detection of myocardial superoxide dismutase(SOD) activity and malondialdehyde(MDA) generation capacity.And further testing the changes of AMPK activity in vitro and in vivo after myocardial ischemia-reperfusion injury.Pre-test the mechanism of protective effects of berberine on myocardial ischemia-reperfusion injury in rats.Results:1.Effects of berberine on isolated rat myocardial ischemia and reperfusion hemodynamics:30min ischemia followed by reperfusion for 30min caused the reduction of left ventricular function.LVDP,±dp/dt were significantly lower after ischemia,has been recovered after reperfusion,but were significantly lower than the level before ischemia;LVEDP were rapidly increased during 2min to 5min of reperfusion.Despite the decline after reperfusion for 30min,LVEDP were significantly higher than the level before ischemia.Berberine(100mg/kg) oral administration in advance for 10 days.LVDP and +dp/dt were recovered 75% after ischemia-reperfusion(P<0.01),-dp/dt were recovered 69%(P<0.01),LVEDP were decreased 29% compared with ischemia-reperfusion group(P<0.01).2.Effects of Berberine on the block of the left anterior desending coronary artery in rats induced ventricular arrhythmia:After the ligation of the rats left anterior desending coronary artery,5min began to arrhythmia.The initial arrhythmia by premature ventricular contractions.Arrhythmia occurs in frequent during 10min to 15min.Malignant arrhythmia decreased blood pressure significantly particularly such as ventricular tachycardia and ventricular fibrillation and seriously affected the heart's blood perfusion.Only a small number of arrhythmia occurs in the beginning of reperfusion during 0min to 5min.Berberine group decreased premature ventricular contractions and reduced the incidence and the duration of ventricular tachycardia and ventricular fibrillation compared with the model group with significant difference(P<0.05).3.Effects of Berberine on myocardial infarct size of acute myocardial ischemia-reperfusion injury:The AAR/LV% was no significant difference between the berberine group and the model group.Ber group IS/LV% and IS/AAR% were lower than model group(P<0.05 or P<0.01).Evans blue and TTC staining of myocardial general picture showing risk area(AAR)with a blood perfusion(blue dye),infarct area(white) and non-infarct area(red).We can see Ber group significantly reduced IS area visually.4.Effects of berberine on isolated and in vivo oxygen free radicals during myocardial ischemia-reperfusion injury:Berberine significantly decreased the lipid peroxidation product MDA and increased SOD activity.So as to reduce the lipid peroxidation damage,anti-oxygen free radicals to protect the myocardial ischemia-reperfusion injury.5.Effects of berberine on isolated and in vivo myocardial ischemia-reperfusion AMPK activity:P-AMPK protein expression is increasing after ischemia- reperfusion.Berberine treatment reduced the P-AMPK protein expression thereby protecting myocardial injury.Conclusion:Effects of berberine on isolated rat myocardial ischemia-reperfusion injury has a protective effect,especially has significant improvement on reperfusion injury of left ventricular function.Berberine significantly reduced the incidence and the duration of arrhythmias in rats in vivo acute myocardial ischemia and increased the tolerance ability of ventricular tachycardia and ventricular fibrillation.Berberine significantly reduced the myocardial infarct size of acute myocardial ischemia-reperfusion injury and enhanced the anti-ischemic myocardial injury capacity.And this protection may be induced by enhancing the body's ability to reduce myocardial oxygen free radical damage and the regulation of myocardial ischemia-reperfusion tissue expression of AMPK activity and thus play its role in myocardial protection.