Abstract:
AimTo investigate the protective effect of lumbrokinase against myocardial ischemia and to further explore its underlying mechanisms. MethodsThe effect of lumbrokinase on myocardial ischemia was observed by a model of acute myocardial infarction due to permanent ligation of the left anterior descending coronary artery in rats. Patch-clamp technique and laser scanning confocal microscopy were utilized to study the action of lumbrokinase on L-type calcium current (
ICa-L) and intracellular calcium concentration ([Ca
2+]
i). ResultsLumbrokinase decreased the infarct size of myocardium in a dose-dependent manner. The inhibitory rate of lumbrokinase at the dose of 20, 40 and 80 mg·kg
-1 was 7.7%, 34.6% and 46.2%, respectively. The electrophysiological studies displayed that, at +10 mV, the
ICa-L was markedly reduced from (-14.42±1.53) pA/pF to (-11.33±1.40) pA/pF (decreased by 21.4%,
P<0.01) and (-9.92±1.31) pA/pF (decreased by 36.5%,
P<0.01) by lumbrokinase (10 and 50 μmol·L
-1), respectively. Confocal experiments showed that 10 μmol·L
-1 lumbrokinase showed no obvious effects on [Ca
2+]
i at resting states (
P>0.05). However, the increase of [Ca
2+]
i induced by 60 mmol·L
-1 KCl was distinctly limited by 10 μmol·L
-1 lumbrokinase (
P<0.01). Within 240 s, the no obvious peak value of fluorescent intensity (FI) was shown. ConclusionLumbrokinase showed protective action against myocardial infarction in rats. The possible mechanisms of anti-ischemia could be attributed to decreasing
ICa-L and [Ca
2+]
i of ventricular myocytes in rats.