Schneider S, Chen W, Hou J, Steenbergen C, Murphy E
Laboratory of Signal Transduction, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina, 27709, USA.
Am J Physiol Heart Circ Physiol. 2001 Feb;280(2):H499-508. doi: 10.1152/ajpheart.2001.280.2.H499.
We examined the effect of inhibition of p38 mitogen-activated protein kinase (MAPK) alpha/beta during ischemia and preconditioning by using the inhibitor SB-202190. Isolated rat hearts were perfused with Krebs-Henseleit buffer, while left ventricular developed pressure (LVDP) and (31)P nuclear magnetic resonance spectra were acquired continuously. After 20 min of ischemia and 25 min of reperfusion, recovery of LVDP in untreated hearts was 32 +/- 4%, whereas hearts treated with SB-202190 5 min before ischemia recovered 59 +/- 7% of their pretreatment LVDP. Preconditioning improved functional recovery to 65 +/- 5%, which was unaffected by SB-202190 treatment, added either throughout the preconditioning protocol (56 +/- 5% recovery) or during the final reperfusion period of preconditioning (71 +/- 11% recovery). Necrosis was assessed after 40 min of ischemia and 2 h of reperfusion using 2,3,5-triphenyltetrazolium chloride (TTC) staining and creatine kinase release. The untreated group had 54 +/- 8% necrotic myocardium, whereas the SB-202190-treated group had 32 +/- 7% and the preconditioned group had 21 +/- 4% necrotic tissue by TTC staining.
我们使用抑制剂SB - 202190研究了在缺血和预处理过程中抑制p38丝裂原活化蛋白激酶（MAPK）α/β的作用。将离体大鼠心脏用Krebs - Henseleit缓冲液灌注，同时连续采集左心室舒张末压（LVDP）和（31）P核磁共振波谱。缺血20分钟和再灌注25分钟后，未处理心脏的LVDP恢复率为32±4%，而在缺血前5分钟用SB - 202190处理的心脏恢复到预处理前LVDP的59±7%。预处理可将功能恢复提高到65±5%，这不受SB - 202190处理的影响，无论是在整个预处理方案中添加（恢复率为56±5%）还是在预处理的最后再灌注期添加（恢复率为71±11%）。在缺血40分钟和再灌注2小时后，使用2,3,5 - 三苯基氯化四氮唑（TTC）染色和肌酸激酶释放评估坏死情况。通过TTC染色，未处理组有54±8%的心肌坏死，而SB - 202190处理组有32±7%，预处理组有21±4%的坏死组织。
