Improved functional recovery of ischemic rat hearts due to singlet oxygen scavengers histidine and carnosine
Improved functional recovery of ischemic rat hearts due to singlet oxygen scavengers histidine and carnosine
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DOI：
10.1006/jmcc.1998.0850
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发表时间：
1999-01-01
影响因子：
5
通讯作者：
Bobst, AM
中科院分区：
文献类型：
--
作者：
Lee, JW;Miyawaki, H;Bobst, AM
活性氧（reactive oxygen species，ROS）参与缺血再灌注损伤的研究越来越多，但对ROS的检测一直是个难题。本研究采用电子顺磁共振（electron parametric resonance，EPR）技术，在体外研究了组氨酸和肌肽对单线态氧（O-1（2））的相对猝灭作用（β-丙氨酰-L-组氨酸），利用受阻仲胺2，2，6，6-四甲基-4-哌啶酮HCl（4-氧代-TEMP）。组氨酸和肌肽对离体灌流大鼠心脏功能恢复的相对影响也进行了研究。以左心室发展压（LVDP）为指标评价功能恢复情况。左心室压力的一阶导数（dP/dt）、心率（HR）和冠状动脉流量（CF）。EPR测量和Stern-Volmer图显示，在维拉中，400 μ M肌肽淬灭O-1（2）的效率是等摩尔组氨酸的两倍。此外，10 mM组氨酸比1 mM组氨酸显著改善离体大鼠心脏的功能恢复。此外，ImM肌肽比等摩尔组氨酸显著地改善功能恢复，并且与IOmM组氨酸一样有效。使用1 mM甘露醇（一种已知的羟基自由基清除剂）的实验未显示出相对于对照心脏的功能恢复改善，从而降低了羟基自由基是主要损伤物质的可能性。另一方面，组氨酸和肌肽对离体大鼠心脏功能恢复的改善与它们在体外的相对O-1（2）淬灭效果之间的相关性，为O-1（2）作为ROS参与再灌注损伤提供了间接证据。(C)北京：科学出版社.
There is increasing evidence that reactive oxygen species (ROS) contribute to post-ischemic reperfusion injury, but determination of the specific ROS involved has proven elusive, In the present study electron paramagnetic resonance (EPR) spectroscopy was used in vitro to measure the relative quenching of singlet oxygen (O-1(2)) by histidine and carnosine (beta-alanyl-L-histidine) utilizing the hindered secondary amine 2,2,6, 6-tetramethyl-4-piperidone HCl (4-oxo-TEMP). The relative effect of histidine and carnosine on functional recovery of isolated perfused rat hearts was also studied. Functional recovery was measured by left ventricular developed pressure (LVDP). first derivative of left ventricular pressure (dP/dt), heart rate (HR) and coronary flow (CF). EPR measurements and Stern-Volmer plots showed that 400 mu M carnosine quenched O-1(2) twice as effectively as equimolar histidine in villa, Moreover, 10 mM histidine improved functional recovery of isolated rat hearts significantly more than 1 mM histidine. Furthermore, 1 mM carnosine improved functional recovery significantly more than equimolar histidine and as effectively as 10 mM histidine. Experiments with 1 mM mannitol, a known hydroxyl radical scavenger, did not show an improvement in functional recovery relative to control hearts, thereby decreasing the likelihood that hydroxyl radicals are the major damaging species. On the other hand, the correlation between improved functional recovery of isolated rat hearts with histidine and carnosine and their relative O-1(2) quenching effectiveness in vitro, provides indirect evidence for O-1(2) as ROS participating in reperfusion injury. (C) 1999 Academic Press.