Lee Woo-Yong, Lee Sun-Mee
College of Pharmacy, Sungkyunkwan University, Suwon-si 440-746, South Korea.
Shock. 2005 Oct;24(4):370-5. doi: 10.1097/01.shk.0000175895.33415.cd.
This study examined the effect of ischemic preconditioning (IPC) in protecting against a hepatic ischemia/reperfusion (I/R) injury, with particular focus on mitochondrial damage. Rat liver was preconditioned by 10 min of ischemia and 10 min of reperfusion. Immediately after IPC, liver was subjected to 90 min of sustained ischemia followed by 5 h of reperfusion. The hepatic I/R increased serum aminotransferase activity and mitochondrial lipid peroxidation 5 h after reperfusion. IPC attenuated these increases. Whereas the mitochondrial glutathione content and glutamate dehydrogenase activities were lower in the I/R group, these decreases were attenuated by IPC. During IPC, the tissue peroxide levels increased after 10 min of ischemia and were normalized after 10 min of reperfusion. In association with the IPC-derived transient increase in the peroxide levels, the significant production of peroxides observed at 10 min of reperfusion after 90 min of ischemia was attenuated. Furthermore, whereas the mitochondria isolated from rat liver after 5 h of reperfusion were rapidly swollen, the swelling rate was attenuated in the mitochondria from rat liver subjected to IPC before the sustained ischemia. The hepatic ATP and adenosine levels were 38% and 46% lower during the reperfusion, respectively. These decreases were attenuated by IPC. Thus, these results suggest that IPC protects the mitochondria against the deleterious effects of I/R, and this protection is associated with the reduced oxidative stress.
本研究检测了缺血预处理(IPC)对肝缺血/再灌注(I/R)损伤的保护作用,尤其关注线粒体损伤。大鼠肝脏经10分钟缺血和10分钟再灌注进行预处理。IPC后立即对肝脏进行90分钟持续缺血,随后再灌注5小时。肝I/R使再灌注5小时后血清转氨酶活性和线粒体脂质过氧化增加。IPC减弱了这些增加。I/R组线粒体谷胱甘肽含量和谷氨酸脱氢酶活性较低,而IPC减弱了这些降低。在IPC期间,缺血10分钟后组织过氧化物水平升高,再灌注10分钟后恢复正常。与IPC引起的过氧化物水平短暂升高相关,缺血90分钟后再灌注10分钟时观察到的过氧化物大量产生减弱。此外,再灌注5小时后从大鼠肝脏分离的线粒体迅速肿胀,而在持续缺血前经IPC处理的大鼠肝脏线粒体中肿胀速率减弱。再灌注期间肝脏ATP和腺苷水平分别降低38%和46%。IPC减弱了这些降低。因此,这些结果表明IPC保护线粒体免受I/R的有害影响,且这种保护与氧化应激降低有关。