Protective Effect And Mechanism Of Saffronic Acid Modified On Myocardial Ischemia-Reperfusion Injury

Myocardial ischemia-repertusion is one of the ways to stop myocardial necrosis,however,reperfusion itself may aggravate myocardial damage after ischemia.Therefore,the development of drugs for the treatment of myocardial ischemia-reperfusion injury is of great significance.GX is a compound obtained by structural modification of saffronic acid.In this paper,the protective effects of GX on myocardial ischemia-reperfusion injury and its possible mechanism of action were observed at two levels:cell level and animal level.At the cellular level,the hypoxia/reoxygenation injury model was established by drug-induced H9c2 cardiomyocytes.The hypoxia/reoxygenation model was successfully established by cell morphology.The cell viability was detected by CCK-8 method.Hoechst 33342 staining method was used.The apoptosis was detected and the intracellular ROS level was detected by fluorescent probe method.The effect of GX on hypoxia/reoxygenation injury of cardiomyocytes was observed.The results showed that 10 μmol/L GX could significantly improve cell viability,improve cardiomyocyte apoptosis and decrease intracellular reactive oxygen species,indicating that GX can improve myocardial cell injury induced by hypoxia/reoxygenation to some extent.At the animal level,a model of myocardial ischemia-reperfusion injury in rats was established(ischemia time 30 min,reperfusion 120 min),and sham operation group,model group,and positive drug safflower yellow pigment group(20 mg/kg)were established.,iv)and GX high,medium and low dose groups(9,6,3 mg/kg,iv);myocardial infarct size was determined by TTC staining;small animal ultrasound imaging system,PowerLab data recording analysis system for detecting cardiac function;The content of CK,LDH,SOD,MDA,TNF-α,IL-1β,IL-6 in rat plasma was determined by the corresponding kits.The real-time quantitative PCR method was used to detect NOX2 and NOX4 in uninfarcted left ventricular myocardium.Changes in TNF-α,IL-1β,and IL-6 gene expression.The experimental results show that compared with the model group,GX medium and high dose groups can significantly reduce myocardial infarct size,reduce LVEDP,and increase hemodynamic parameters such as Max dp/dt,Min dp/dt and Heart-Rate.Significantly increased EF,FS and other heart color ultra-evaluation indicators;key kinase results showed that GX high dose group can significantly reduce the activity of CK and LDH in rat plasma,oxidative stress indicators show that GX high dose group can significantly reduce MDA level It can simultaneously increase SOD activity and inhibit the levels of inflammatory factors TNF-α,IL-6 and IL-1β in plasma.Real-time quantitative PCR results show that GX high dose group can effectively down-regulate NOX2,NOX4 and inflammation.Gene expression of the factors TNF-a,IL-6 and IL-1β.Based on the above results,GX as a saffron acid modification can improve myocardial cell injury induced by hypoxia/reoxygenation at the cellular level;at the animal level,myocardial infarction caused by ischemia-reperfusion can be significantly reduced,and cardiac function can be improved.Therefore,it plays a protective role against damaged myocardium,and its mechanism of action is related to the resistance to oxygen free radicals and the reduction of the expression of inflammatory factors in myocardial tissue.