| Objective：To study the protective effects of fasidotril on myocardial ischemia-reperfusion injury in rats and its mechanisms.Methods： Healthy male SD rats, weighing280±20g, were randomly divided intofour groups: shamoperation group, ischemia-reperfusion group, low-dose group(2.5mg/kg), high-dose group (25mg/kg),10rats in each group. Myocardialischemia-reperfusion injury model in rats was established by ligating the left anteriordescending coronary artery for30min, followed by reperfusion for120min. Theindexes of cardiac systolic and diastolic function, such as LVSP, LVEDP, HR,+dp/dtmax and-dp/dtmax were recorded by BL-420E biological function experimentsystem. The level of AngII in plasma and myocardial tissuewas measured accordingto ELISA Kit, and the expression of AngII and ACE expression was detected byimmunohistochemical method.Results：(1) HR in ischemia-reperfusion group was decreasedas compared toshamoperation group (P<0.01). Compared with ischemia-reperfusion group, fasidotrilcould increase HR significantly (P<0.05), and with the increase of the dose, HRamplitude increased. Therehad no significant difference between high-dose group andsham operation group (P>0.05).(2) Compared with sham operation group, the levels of left ventricular systolic bloodpressure(LVSP) in the model group, left heart interior maximum pressure riserate(+dp/dtmax), left heart indoor pressure maximum decline rate(-dp/dtmax) weresignificantly decreased, the levels of left ventricular end-diastolic pressure(LVEDP)were significantly increased(P<0.01). Compared with ischemia-reperfusion group, thelevels of LVSP,+dp/dtmax,-dp/dtmax in fasidotril groups were signiifcantlyincreased, the levels of LVEDP were signiifcantly decreased (P<0.05).(3) Compared with sham operation group,the AngII level in plasma and myocardialtissue and the density of AT1and ACE positive expression in myocardium wereincreased significantly in ischemia-reperfusion group,which showed that RAS wasmarkedly activatedafter myocardial ischemia-reperfusion.Compared with ischemia- reperfusion group,fasidotril treatment could significantly reverse above changes,decrease the level of AngII in plasma and myocardial tissue (P<0.05), inhibit thepositive expression of AT1and ACE in myocardium, and the effect was dose-dependent (P<0.05).Conclusion：(1) The levels of AngII, ACE and AT1in circulation and myocardiallocal tissue were increased significantly after myocardial ischemia-reperfusion, andthe activation of the RAS may be involved in the pathophysiology of myocardialischemia-reperfusion injury.(2) Fasidotril has a protective effect on myocardial ischemia-reperfusion injury andthe mechanism may be related with inhibition of angiotensin converting enzymeactivity and the reduction of circulation and myocardial angiotensin II formation. |
PDF Full Text Request