Experimental study that trimetazidine inhibits Fas/FasL pathway to relieve the myocardial ischemia reperfusion injury in rats

摘要

Objective: To study the protective effect and molecular mechanism of trimetazidine on myocardial ischemia reperfusion injury in rats. Methods: Adult male SD rats were chosen as the experimental animals and randomly divided into control group, ischemia reperfusion group and trimetazidine group, and myocardial ischemia reperfusion models were established and then given intraperitoneal injection of trimetazidine hydrochloride for intervention. The expression levels of Fas/FasL pathway molecules as well as the contents of inflammatory and oxidative stress molecules in the myocardium, and the contents of myocardial enzymes in the blood circulation were measured 120 min after reperfusion. Results: Fas, FasL, Caspase-8 and Caspase-3 mRNA expression as well as NK-κB, TNF-α, ICAM-1, IL-17, IL-23, NOX2, NOX4, AOPP and MDA contents in myocardium, and LDH, CK and CK-MB contents in blood circulation of ischemia reperfusion group were significantly higher than those of control group, and Fas, FasL, Caspase-8 and Caspase-3 mRNA expression as well as NK-κ B, TNF-α, ICAM-1, IL-17, IL-23, NOX2, NOX4, AOPP and MDA contents in myocardium, and LDH, CK and CK-MB contents in blood circulation of trimetazidine group were significantly lower than those of ischemia reperfusion group; LDH, CK and CK-MB contents in blood circulation as well as NK-κB, TNF-α, ICAM-1, IL-17, IL-23, NOX2, NOX4, AOPP and MDA contents in myocardium of trimetazidine group were positively correlated with Fas and FasL mRNA expression. Conclusion: Trimetazidine can inhibit Fas/FasL pathway to reduce the myocardial damage caused by inflammatory response and oxidative stress response during myocardial ischemia reperfusion in rats.