Uchinami Hiroshi, Yamamoto Yuzo, Kume Makoto, Yonezawa Kei, Ishikawa Yasuhide, Taura Kojiro, Nakajima Akio, Hata Koichiro, Yamaoka Yoshio
Department of Gastroenterological Surgery, Graduate School of Medicine, Kyoto University, Kyoto 606 - 8507, Japan.
Am J Physiol Gastrointest Liver Physiol. 2002 Jun;282(6):G962-71. doi: 10.1152/ajpgi.00466.2001.
Hepatic ischemia-reperfusion (I/R) injury continues to be a fatal complication after liver surgery. Heat shock (HS) preconditioning is an effective strategy for protecting the liver from I/R injury, but its exact mechanism is still unclear. Because the activation of nuclear factor-kappaB (NF-kappaB) is an important event in the hepatic I/R-induced inflammatory response, the effect of HS preconditioning on the pathway for NF-kappaB activation was investigated. In the control group, NF-kappaB was activated 60 min after reperfusion, but this activation was suppressed in the HS group. Messenger RNA expressions of proinflammatory mediators during reperfusion were also reduced with HS preconditioning. Concomitant with NF-kappaB activation, NF-kappaB inhibitor I-kappaB proteins were degraded in the control group, but this degradation was suppressed in the HS group. This study shows that HS preconditioning protected the liver from I/R injury by suppressing the activation of NF-kappaB and the subsequent expression of proinflammatory mediators through the stabilization of I-kappaB proteins.
肝缺血再灌注(I/R)损伤仍是肝脏手术后的致命并发症。热休克(HS)预处理是保护肝脏免受I/R损伤的有效策略,但其确切机制仍不清楚。由于核因子κB(NF-κB)的激活是肝I/R诱导的炎症反应中的一个重要事件,因此研究了HS预处理对NF-κB激活途径的影响。在对照组中,再灌注60分钟后NF-κB被激活,但在HS组中这种激活受到抑制。HS预处理也降低了再灌注期间促炎介质的信使核糖核酸表达。与NF-κB激活同时,对照组中NF-κB抑制剂I-κB蛋白降解,但在HS组中这种降解受到抑制。本研究表明,HS预处理通过稳定I-κB蛋白抑制NF-κB的激活以及随后促炎介质的表达,从而保护肝脏免受I/R损伤。