TPEN attenuates hepatic apoptotic ischemia/reperfusion injury and remote early cardiac dysfunction
TPEN attenuates hepatic apoptotic ischemia/reperfusion injury and remote early cardiac dysfunction
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DOI：
10.1007/s10495-005-6061-z
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发表时间：
2005-01-01
期刊：
影响因子：
7.2
通讯作者：
Vidne, BA
中科院分区：
文献类型：
--
作者：
Hochhauser, E;Ben-Ari, Z;Vidne, BA
肝脏缺血/再灌注损伤过程中心脏活性物质的释放产生毒性自由基，造成肝脏和远端心脏损伤。本研究的目的是确定TPEN，一种有效的铁螯合剂，是否能改善凋亡性肝和心功能损伤。实验分三组：（1）Krebs-Henseleit液连续灌流;（2）缺血120 min再灌注15 min;（3）缺血前给予TPEN。用再灌注肝脏的流出物灌注离体心脏65分钟。结果显示，TPEN给药减少了去甲肾上腺素、肾上腺素、多巴胺、前列腺素E2和血管紧张素II的释放，降低了肝内半胱天冬酶-3活性，并降低了平均肝细胞凋亡指数（TUNEL测定）（p= 0.001）。缺血后肝脏流出物灌注导致左心室收缩和冠状动脉流量短暂增加15分钟（p< 0.05），随后1小时心功能下降。TPEN降低了左心室收缩的瞬时升高（p< 0.05），但不能防止随后的心功能下降。总之，TPEN通过调节半胱天冬酶-3样活性来减轻缺血后凋亡性肝损伤，并减少从肝脏释放的心脏活性物质。
The release of cardioactive substances during hepatic ischemia/reperfusion injury generates toxic free radicals that inflict hepatic and remote cardiac damage. The aim of the study was to determine whether TPEN, a potent iron chelator, ameliorates the apoptotic hepatic and cardiac function injuries. Three groups of isolated rat livers were studied: ( 1) continuously perfused with Krebs-Henseleit solution; ( 2) subjected to 120 min of ischemia and 15 min of reperfusion; ( 3) as in group 2, with TPEN administered prior to ischemia. Isolated hearts were perfused for 65 min with the effluent of the reperfused livers. Results showed that TPEN administration reduced the release of norepinephrine, epinephrine, dopamine, prostaglandin E2 and angiotensin II, decreased intrahepatic caspase-3 activity, and decreased the mean hepatocyte apoptotic index ( TUNEL assay) ( p= 0.001). Perfusion with post-ischemic hepatic effluent caused a transient 15-min increase in left ventricular contraction and coronary flow ( p< 0.05), followed by a decrease in cardiac function at one hour. TPEN reduced the transient elevation in left ventricular contraction p< 0.05), but did not prevent the subsequent decrease in cardiac function. In conclusion, TPEN attenuates post-ischemic apoptotic hepatic injury by modulating caspase-3-like activity and reduces the cardioactive substances released from the liver.