Yamamoto Y, Kume M, Yamaoka Y
Department of Gastroenterological Surgery, Kyoto University, Graduate School of Medicine, Japan.
Recent Results Cancer Res. 1998;147:157-72. doi: 10.1007/978-3-642-80460-1_15.
Cells primed by sublethal stress transiently overproduce heat shock proteins (HSPs) and thereby develop tolerance to the next lethal stress. This response in organisms is called the stress response and involves the induction of HSPs. To assist the liver in developing tolerance for warm ischemia-reperfusion injury, which sometimes jeopardizes the patients after extended surgery for malignancies with vascular invasion in the liver, basic experiments to activate the stress response using stress preconditioning were performed. Heat shock preconditioning in rat livers has been shown to induce tolerance against warm ischemia-reperfusion injury in normal, fibrotic, and steatotic livers. Ischemic preconditioning using short-term Pringle's maneuver and pharmacological preconditioning using doxorubicin were also effective. In rats, heat shock preconditioning protected livers from free radical injury induced by the oral administration of carbon tetrachloride. The above data were supported by animal survival, suppression of serum transaminase levels, and improved energy status of the liver after intervention. Increased production of HSP72 was observed after preconditioning. In addition, the significance of HSP production as a stress parameter was demonstrated during the reperfusion of congested portal blood to the ischemic liver. The ill effect of congested portal blood could not be detected by conventional parameters but was detected by observing the increase in HSP72 production. Stress preconditioning seems to be a promising strategy to counter the damaging effect of hepatic warm ischemia during liver surgery and liver perfusion.
亚致死性应激引发的细胞会短暂地过度产生热休克蛋白（HSPs），从而对下一次致死性应激产生耐受性。生物体中的这种反应被称为应激反应，涉及HSPs的诱导。为了帮助肝脏对温暖缺血-再灌注损伤产生耐受性，这种损伤有时会在对肝脏有血管侵犯的恶性肿瘤进行长时间手术后危及患者，我们进行了一些基础实验，通过应激预处理来激活应激反应。大鼠肝脏的热休克预处理已被证明可在正常、纤维化和脂肪变性的肝脏中诱导对温暖缺血-再灌注损伤的耐受性。使用短期普林格尔手法进行的缺血预处理以及使用阿霉素进行的药物预处理也有效。在大鼠中，热休克预处理可保护肝脏免受口服四氯化碳诱导的自由基损伤。上述数据得到了动物存活率、血清转氨酶水平的抑制以及干预后肝脏能量状态改善的支持。预处理后观察到HSP72的产生增加。此外，在将充血的门静脉血再灌注到缺血肝脏的过程中，证明了HSP产生作为应激参数的重要性。充血的门静脉血的不良影响无法通过传统参数检测到，但通过观察HSP72产生的增加可以检测到。应激预处理似乎是一种有前景的策略，可以对抗肝脏手术和肝脏灌注期间肝脏温暖缺血的破坏作用。
