Basgut Bilgen, Aypar Eda, Basgut Ertug, Akin K Okhan, Kilic Nedret, Cakici Iclal
Gazi University, Faculty of Pharmacy, Department of Pharmacology, Etiler, Ankara, Turkey.
Arch Pharm Res. 2008 Oct;31(10):1257-63. doi: 10.1007/s12272-001-2104-3. Epub 2008 Oct 29.
The aim of the present study was to investigate the mechanism of effect of 3-nitropropionic acid-(3-NP) induced late preconditioning in rat heart. For this purpose 20-30 min before 3-NP (20 mg/kg, i.p.) injection, the rats were treated intraperitoneally with 5-hydroxydecanoate (40 mg/kg, 5-HD, mitochondrial K(ATP)-channel blocker), L-NAME (100 mg/kg, NOS inhibitor), N-2-mercaptopropionylglycine (100 mg/kg, MPG, free radical scavenger), or superoxide dismutase+catalase (10000+10000 IU/kg, SOD+CAT). Control rats received saline only without 3-NP pretreatment. After two days, hearts were isolated and perfused at a constant pressure in a Langendorff apparatus. 15-min global ischemia followed by 30-min reperfusion was applied to all hearts. Pretreatment of 3-NP significantly reduced infarct size, creatine kinase-MB (CK-MB), lactate dehydrogenase (LDH) levels, and incidence of ventricular tachycardia (VT) compared with the control group receiving saline only. 5-HD, L-NAME, MPG, or SOD+CAT treatment statistically reversed 3-NP-induced reduction in infarct size. Although CK-MB, LDH levels, and incidence of VT were also reduced by L-NAME, MPG, or SOD+CAT treatment, only 5-HD significantly inhibited beneficial effects of 3-NP on all of the parameters above. These results showed that mito-K(ATP) channels play a pivotal role in late preconditioning effect of 3-NP in the isolated rat heart. However, other mediators such as reactive oxygen species and NO may be, at least in part, involved in mechanisms of this effect.
本研究的目的是探讨3-硝基丙酸（3-NP）诱导大鼠心脏延迟预处理的作用机制。为此，在注射3-NP（20mg/kg，腹腔注射）前20-30分钟，给大鼠腹腔注射5-羟基癸酸（40mg/kg，5-HD，线粒体ATP敏感性钾通道阻滞剂）、L-硝基精氨酸甲酯（100mg/kg，NOS抑制剂）、N-2-巯基丙酰甘氨酸（100mg/kg，MPG，自由基清除剂）或超氧化物歧化酶+过氧化氢酶（10000+10000IU/kg，SOD+CAT）。对照组大鼠仅接受生理盐水，未进行3-NP预处理。两天后，分离心脏并在Langendorff装置中恒压灌注。所有心脏均进行15分钟全心缺血，随后再灌注30分钟。与仅接受生理盐水的对照组相比，3-NP预处理显著减小了梗死面积，降低了肌酸激酶-MB（CK-MB）、乳酸脱氢酶（LDH）水平以及室性心动过速（VT）的发生率。5-HD、L-硝基精氨酸甲酯、MPG或SOD+CAT处理在统计学上逆转了3-NP诱导的梗死面积减小。尽管L-硝基精氨酸甲酯、MPG或SOD+CAT处理也降低了CK-MB、LDH水平以及VT的发生率，但只有5-HD显著抑制了3-NP对上述所有参数的有益作用。这些结果表明，线粒体ATP敏感性钾通道在3-NP对离体大鼠心脏的延迟预处理作用中起关键作用。然而，其他介质如活性氧和一氧化氮可能至少部分参与了这种作用的机制。
