The Effects Of NAD~+and NAD~+ Dependent Enzymes On Myocardial Ischemia And The Underlying Mechanisms

Coronary heart disease is one of the major threats to human health and life with increasing morbidity and mortality.Acute myocardial infarction is the most serious coronary heart disease.Although interventional therapy is largely available around the world,the ischemia reperfusion injury remains unsolved.Cumulative evidence has suggested that NAD~+plays a substantial role in terms of redox,calcium,energy dysfunction,mitochondria function.Since ischemia reperfusion injury is also significantly affected by those mechanisms.Thus,we hypothesis that NAD~+may provide profound protective effect in myocardial ischemia reperfusion injury.In the present study,we found that 10-20 mg/kg NAD~+can dose-dependently protect the heart from I/R injury.In which,20 mg/kg NAD~+can decrease I/R induced infarct size by 85%.We further found that NAD~+can also reduce the level of serum cTnI.The underlying mechanism of NAD~+protects I/R injury can be attributed to enhance antioxidant and antiapoptosis.NAD~+can reverse the increase of Bax and caspase-3 and decrease of Bcl-XL which induced by I/R injury.NAD~+can also provide protection for protein level and activity of SOD.Which can eliminate the excessive ROS;maintain a balance of antioxidation and oxidation.NAD~+decrease apoptosis change by the means of enhance antioxidative.In conclusion,our study firstly found that NAD~+can protect I/R injury in vivo.The mechanism of NAD~+protects I/R injury can be explained by enhanced antioxidative and antiapoptosis.NAD~+can be a novel potential drug in myocardial ischemia reperfusion injury.