Guo Y, Wu W J, Qiu Y, Tang X L, Yang Z, Bolli R
Experimental Research Laboratory, Division of Cardiology, University of Louisville, Louisville, Kentucky 40292, USA.
Am J Physiol. 1998 Oct;275(4):H1375-87. doi: 10.1152/ajpheart.1998.275.4.H1375.
It is unknown whether ischemic preconditioning (PC; either early or late) occurs in the mouse. The goal of this study was to answer this question and to develop a reliable and physiologically relevant murine model of both early and late ischemic PC. A total of 201 mice were used. In nonpreconditioned open-chest animals subjected to 30 min of coronary occlusion followed by 24 h of reperfusion, infarct size (tetrazolium staining) averaged 52% of the region at risk. When the 30-min occlusion was performed 10 min after a PC protocol consisting of six cycles of 4-min occlusion and 4-min reperfusion, infarct size was reduced by 75%, indicating an early PC effect. When the 30-min occlusion was performed 24 h after the same PC protocol, infarct size was reduced by 48%, indicating a late PC effect. In mice in which the 30-min occlusion was followed by 4 h of reperfusion, infarct size was similar to that observed after 24 h of reperfusion, indicating that a 4-h reperfusion interval is sufficient to detect the final extent of cell death in this model. Fundamental physiological variables (body temperature, arterial oxygenation, acid-base balance, heart rate, and arterial pressure) were measured and found to be within normal limits. Taken together, these results demonstrate that, in the mouse, a robust infarct-sparing effect occurs during both the early and the late phases of ischemic PC, although the early phase is more powerful. This murine model is physiologically relevant, provides reliable measurements, and should be useful for elucidating the cellular mechanisms of ischemic PC in genetically engineered animals.
尚不清楚小鼠是否会发生缺血预处理（PC；早期或晚期）。本研究的目的是回答这个问题，并建立一个可靠的、与生理相关的早期和晚期缺血PC小鼠模型。总共使用了201只小鼠。在未进行预处理的开胸动物中，冠状动脉闭塞30分钟后再灌注24小时，梗死面积（四氮唑染色）平均为危险区域的52%。当在由六个4分钟闭塞和4分钟再灌注周期组成的PC方案后10分钟进行30分钟闭塞时，梗死面积减少了75%，表明早期PC效应。当在相同的PC方案后24小时进行30分钟闭塞时，梗死面积减少了48%，表明晚期PC效应。在冠状动脉闭塞30分钟后再灌注4小时的小鼠中，梗死面积与再灌注24小时后观察到的相似，表明4小时的再灌注间隔足以检测该模型中细胞死亡的最终程度。测量了基本生理变量（体温、动脉氧合、酸碱平衡、心率和动脉压），发现其在正常范围内。综上所述，这些结果表明，在小鼠中，缺血PC的早期和晚期均出现显著的梗死面积减少效应，尽管早期效应更强。这种小鼠模型与生理相关，提供了可靠的测量结果，并且应该有助于阐明基因工程动物中缺血PC的细胞机制。
