Protective Effects And Mechanism Of DhHP-6 On Myocardium Cell Injury Induced By Oxidative Stress

The incidence,mutilation rate and lethality rate of cardiovascular diseases turn on the increasing trends all over the world in recent years. Ischemic heart disease(IHD)is one of the most common cardiovascular diseases in clinical practice.IHD is caused by coronary blood circulation changes resulting in the imbalance of myocardial supply and demand. Drug therapy is one of important ways to cure myocardial ischemia.Although nitrate,calcium-channel blocker andβ-receptor antagonist are effective in the therapy of myocardial ischemia,they all have some adverse reactions.Studies on the new agents used to treat myocardium ischemia are still a pivotal issue.DhHP-6 is enzyme mimetics of peroxidases made by the method of mimic enzyme . the significance of the peroxidases is in the prevention and therapy of the diseases caused by free radicals, In spite of the therapeutical potential of natural peroxidases,it is severely limited by its source, difficult refinement, instability,molecular mass and other factors; thus enzyme mimetics of peroxidases are desirable. DhHP-6 is reseached by jilin university , its peroxidase activity (2.1x103U·μmol-1)is similar to that of MP-11(4.2x103U·μmol-1).we culture cardiac mytes damagede by hydrogen peroside(H2O2) in vitro simulating the oxidative stress model for further approaching the effect of DhHP-6. The primary cultured cardiac mytes in neonatal rats damaged by hydrogen peroside(H2O2)simulated the oxidative stress model. To research the protective effect and its possible mechanism of DhHP-6 in ischemia-reperfusion injury on the level of cell . These can provide theoretical basis for better, safer using and targeting application of this therapy in clinical treatment.We found numerous fragmentation and crimple of cardiocyte after incubation with 0.3 mmol/L H2O2,at the same time, degade the refactive index of cardiocyte and change the cardiocyte appearance ; The apoptosis cells morphous were observed by hoechst33258 through fluorescence microscope .However, DhHP-6 could protect the above conditon,and Different DhHP-6 dose groups could inhibit H2O2-induced apoptosis in cardiocyte more or less,significantly lower the rate of apoptosis significantly(P<0.001,P<0.05);and different DhHP-6 dose groups could stabilize mitochondria membrane potential,remarkably increased△Ψm (P<0.001,P<0.01) and positively correlated with apoptosis rate.Meanwhile, DhHP-6 could increase SOD activity (P<0.01,P<0.05), low MDA content (P<0.001, P<0.01) in medium and low the leakage content of LDH and CK (P<0.001,P<0.01). The results of ROS showed that DhHP-6 could decrease the content of ROS (P<0.001,P<0.01) .it is explained that DhHP-6 could have the effect of antioxidative stress by improving the possibility of antioxidase activity,inhibitting dose-dependently lipid peroxidation and directly cleaning free radicals on cardiocyte damage . in addition , the apoptosis cardiocyte could be resulted by oxidative stress and free radicals . The experiment showed that DhHP-6 could inhibit the apoptosis of cardiocyte damaged by H202,but but the mechanism will study in future.The present study demonstrated that can DhHP-6 prevent cardiocyte damaged by oxidative stress and showed the mechanism.The study provide the evidence in theory on preventing and cureing heart disease induced by oxidative stress for clinical application .