Eum Hyun-Ae, Cha Young-Nam, Lee Sun-Mee
College of Pharmacy, Sungkyunkwan University, 300 Cheoncheon-Dong, Jangan-Gu, Suwon-Si, Gyeonggi-Do, Republic of Korea.
Biochem Biophys Res Commun. 2007 Jun 29;358(2):500-5. doi: 10.1016/j.bbrc.2007.04.153. Epub 2007 May 2.
This study evaluated the time-dependent modes of cell death that occur during the course of reperfusion after 60 min ischemia. The serum ALT level increased immediately after reperfusion, peaked at 6 h and then declined gradually thereafter. This was supported by the H&E staining of the liver tissues taken at 2 h reperfusion, which revealed massive peri-portal necrosis. The succinate driven mitochondrial-swelling rate, release of cytochrome c into the cytoplasm, increase in caspase-3 activity and TUNEL stained tissue were measured to determine the changes in the biochemical markers of apoptosis. The biochemical markers of apoptosis increased by 2 h of reperfusion, peaked at 6 h and remained elevated throughout the 24 h reperfusion period. Cyclosporin A, an inhibitor of the mitochondrial permeability transition (MPT), inhibited MPT opening, the release of cytochrome c and caspase-3 activation. This indicates that necrotic death occurs particularly in the peri-portal region in the initial period of reperfusion, and delayed apoptotic death occurs primarily in the peri-central region in the liver tissues undergoing I/R.
本研究评估了60分钟缺血后再灌注过程中发生的细胞死亡的时间依赖性模式。再灌注后血清ALT水平立即升高，在6小时达到峰值，随后逐渐下降。这得到了再灌注2小时时采集的肝组织H&E染色的支持，该染色显示大量门周坏死。测量琥珀酸驱动的线粒体肿胀率、细胞色素c释放到细胞质中的情况、caspase-3活性的增加以及TUNEL染色组织，以确定凋亡生化标志物的变化。凋亡生化标志物在再灌注2小时时增加，在6小时达到峰值，并在整个24小时再灌注期保持升高。线粒体通透性转换（MPT）抑制剂环孢素A抑制MPT开放、细胞色素c释放和caspase-3激活。这表明坏死性死亡尤其发生在再灌注初期的门周区域，而延迟性凋亡死亡主要发生在经历缺血/再灌注的肝组织的中央周围区域。
