Abstract
Objective To explore the phenolic tetrahydro-β-carboline-arginine-glycine-aspartic acid (THBCB-RGD) peptidomimetic conjugates’ role in myocardial ischemia-reperfusion injury. Methods Using high performance liquid chromatography (HPLC) method to detect the stability of THBCB-RGD peptidomimetic conjugates. The oxyradical scavenging ability of THBCB-RGD peptidomimetic conjugates was assessed by PC12 cells survive experiment and acetylcholine induced vasodilatation experiment assessment. The antiplatelet aggregation activity of THBCB-RGD peptidomimetic conjugates was evaluated by platelet aggregation exprement. Through the in vivo experiment, we evaluated the antithrombotic activity of THBCB-RGD peptidomimetic conjugates. Next, we constructed the cardiac ischemia reperfusion model and observe the effects of phenolic THBCB-RGD peptidomimetic conjugates on myocardial oxidative stress and myocardial infarction. Results HPLC results show that THBCB-RGD peptidomimetic conjugates has a strong ability of scavenging (exhaustion time: 240 min, 180 min, 240 min; RHBCB: 30 min; P=0.005). NO, H2O2 and ·OH as well as inhibiting platelet aggregation and thrombus formation (P=0.004 or P=0.000). It can also inhibit the aggregation of platelets and the formation of thrombus (P=0.003 or P=0.000). In addition, treatment with phenolic tetrahydro-β-carboline-RGD peptidomimetic conjugates before the heart ischemia-reperfusion injury can decrease the MDA content in myocardium and reduce the myocardial infarction area. Conclusion THBCB-RGD peptidomimetic conjugates showed a strong ability of scavenging oxyradical and anti-thrombosis. Addition, THBCB-RGD peptidomimetic conjugates play a protective role in cardiac ischemia-reperfusion injury by inhibiting oxidative stress and reducing the myocardial infarction area. Key words: Phenolic tetrahydro-β-carboline-arginine-glycine-aspartic acid peptidomimetic conjugates; Ischemia-reperfusion injury; Oxidative stress; Myocardial infarction
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