The Protective Effects Of Gossypol On Myocardial Ischemia/reperfusion Injury In Isolated Rat Hearts And Its Mechanism

BackgroundTo find new drugs from natural products is one of the important method.Gossypol,a qpolyphenol,is one of the main components of cottonseed.Gossypol presents significant anti-inflammatory and immunomodulatory effects.In recent years,with the development of molecular biology,studies on the pharmacological activity of this substance have demonstrated its multiple-targeting effect.Gossypol appears to play an extensive role in inhibiting inflammatory mediators,inhibiting the release of ROS,inhibiting the expression of adhesion molecules,inhibiting the activation and infiltration of neutrophils,and regulating immunity.Presently,no report is available on the ability of Ru to reduce multiple-organ myocardial ischemia/reperfusion injury.ObjectiveIn this research,the protective effect and possible mechanism of Gossypol on isolated myocardial ischemia/reperfusion injury in rats were investigated.Method40 male Sprague-Dawley rats were divided randomly into 4 groups:Blank group,heart ischemia reperfusion group（I/R group）,high and low-dose Gossypol group(40,20 mg.L^-1).The model of the myocardial ischemia/reperfusion injury were established using the Langendorff method.The hemodynamics indexes,cardiac enzymes AST and LDH,inflammatory cytokines（NF-?B、ICAM-1、TNF-?and IL-6）were measured.The effect and mechanism of Gossypol on early-stage MI/R of the oxidative stress response and the JNK/p38 MAPK signal pathway were investigated.ResultExperimental results showed that Gossypol could significantly improve the functional capacity of the heart,reduce the contents of AST,LDH and inflammatory cytokines in reperfused heart tissue,and increase serum superoxide dismutase levels to protect the heart.The mechanism of this substance may involve anti-lipid peroxidation and inhibition of p38 kinase phosphorylation and JNK,and reduction of oxidative stress injury and apoptosis damage induced by MI/R.ConclusionThis researchstudy confirmed that Gossypol gossypol exerts shows extensive anti-MI/R effects.Its mechanism may was related to the interfering with the oxidative stress response and suppressing the JNK/p38 MAPK signal pathway.Therefore,we believed that Gossypol could be used to be a lead compound to prevent or treat myocardial ischemia/reperfusion injury.