蚓激酶的心肌保护作用及机制

目的研究蚓激酶对心肌缺血的保护作用，并进一步探讨其可能机制。方法采用结扎大鼠左冠状动脉前降支制备急性心肌缺血模型，观察蚓激酶对心肌缺血的保护作用；应用全细胞膜片钳和激光扫描共聚焦技术，研究蚓激酶对L-型钙电流(I_Ca-L)和细胞内游离钙离子浓度的影响。结果蚓激酶80，40和20 mg·kg^-1剂量组均可缩小心肌梗死面积。膜片钳研究结果表明，当刺激电压为+10 mV时，10和50 μmol·L^-1蚓激酶使I_Ca-L降低共聚焦结果显示，在静息状态下，10 μmol·L^-1蚓激酶对［Ca²⁺］_i无明显影响；但10 μmol·L^-1蚓激酶对60 mmol·L^-1 KCl诱导的［Ca²⁺］_i升高却有明显抑制作用，并且在整个实验过程中(240 s)并未出现明显的峰值。结论蚓激酶对大鼠心肌缺血具有保护作用，其机制可能与抑制I_Ca-L及下调［Ca²⁺］_i有关。

The cardioprotective effect and mechanism of lumbrokinase

AIM: To investigate the protective effect of lumbrokinase against myocardial ischemia and to further explore its underlying mechanisms. METHODS: The 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 (Ca2+]i). RESULTS: Lumbrokinase 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 x 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 micromol x L(-1)), respectively. Confocal experiments showed that 10 micromol x L(-1) lumbrokinase showed no obvious effects on Ca2+]i at resting states (P > 0.05). However, the increase of Ca2+]i induced by 60 mmol x L(-1) KCl was distinctly limited by 10 micromol x L(-1) lumbrokinase (P <0.01). Within 240 s, the no obvious peak value of fluorescent intensity (FI) was shown. CONCLUSION: Lumbrokinase showed protective action against myocardial infarction in rats. The possible mechanisms of anti-ischemia could be attributed to decreasing ICa-L and Ca2+] of ventricular myocytes in rats.