孙宏丽, 焦军东, 潘振伟, 董德利, 杨宝峰. 蚓激酶的心肌保护作用及机制J. 药学学报, 2006, 41(3): 247-251.
引用本文: 孙宏丽, 焦军东, 潘振伟, 董德利, 杨宝峰. 蚓激酶的心肌保护作用及机制J. 药学学报, 2006, 41(3): 247-251.
SUN Hong-li, JIAO Jun-dong, PAN Zhen-wei, DONG De-li, YANG Bao-feng. The cardioprotective effect and mechanism of lumbrokinaseJ. Acta Pharmaceutica Sinica, 2006, 41(3): 247-251.
Citation: SUN Hong-li, JIAO Jun-dong, PAN Zhen-wei, DONG De-li, YANG Bao-feng. The cardioprotective effect and mechanism of lumbrokinaseJ. Acta Pharmaceutica Sinica, 2006, 41(3): 247-251.

蚓激酶的心肌保护作用及机制

The cardioprotective effect and mechanism of lumbrokinase

  • 摘要: 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(ICa-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ICa-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ICa-L及下调[Ca2+i有关。

     

    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 ([Ca2+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 [Ca2+i at resting states (P>0.05). However, the increase of [Ca2+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 [Ca2+i of ventricular myocytes in rats.

     

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