Reduction of Hepatic Injury after Hepatic Surgery by Advance Induction of Heart Shock Protein and Hepatic Oxygenation

我们已经揭示了肝血流中氧含量的增加改善了肝功能。肝细胞中的热休克蛋白（Heat shock protein，Hsp）与DNA损伤密切相关，其改善依赖于ATP的代谢，提示通过适当的方法诱导肝细胞中Hsp的表达，可用于保护肝脏免受手术损伤。我们计划通过肝氧合和高温诱导肝细胞热休克蛋白来提高肝癌合并肝硬化切除术的安全性。虽然已经进行了许多关于肝储备功能的研究，但其结果用于区分术后潜在肝衰竭的患者，这些患者将被排除在肝切除术之外。针对这类患者，我们试图通过改变肝血流中氧浓度或诱导细胞内Hsp等内在因素来增加肝脏承受手术损伤的储备功能。肝组织中Hsp的含量和分布随肝功能损害程度的不同而变化。43 ℃水浸泡诱导Hsp73在肝细胞中表达，并使其定位于细胞核和细胞质之间。免疫印迹法测定的热休克蛋白诱导量与热休克持续时间和时间有关。在预先诱导Hsp的大鼠中，对肝缺血、内毒素灌注和硫代乙酰胺给药引起的肝损伤具有保护作用。肝静脉回流对肝细胞缺血性损伤有保护作用，提示肝静脉回流可促进肝氧合，提前诱导Hsp表达，提高肝储备功能，值得临床推广应用。

We have already revealed that the increase of oxygen content in the hepatic blood flow improved liver function. It is also reported that the heat shock protein (Hsp) in hepatocyte has close relationship to DNAinjury and its improvement depending on ATP metabolism, which suggests the induction of Hsp in hepatocytes by some suitable method can be useful for protection of the liver from operative insult.On these bases, we made a plan to increase the safety of hepatectomy for hepatoma with cirrhosis by hepatic oxygenation and advance induction of hepatocyte Hsp using hyperthermia. Although many studies on the hepatic functional reserve have been conducted, the results were used for discrimination of the patients with potential hepatic failure after surgery, who are to be excluded from hepatectomy. Focusing on such patients, we attempted to increase the functional reserve of the liver to bear the operative insult by changing the intrinsic factors such as oxygen concentration in the hepatic blood flow or induction of intracellular Hsp.Following results are obtained in this experiment using rats.1). content and localisation of Hsp in the liver changed according to the extent of hepatic dysfunction.2). Hsp73 is induced in the hepatocyte by immersion of the whole body in water of 43 degree (C), and cahnge its location between nucleus andcytoplasm.3). Induction of Hsp in volume measured by immunobloting cahnged depending on the duratioon and time of heat exposure.4). In the rats with advance induction of Hsp, the liver injury by hepatic ischemia, endotoxin infusion and administration of thioacetamide could be protected.5). Hepatic venous back flow seemed to protect hepatocyte from ischemic injury by inflow occlusion.These results can support the significance of hepatic oxygenation and advance induction of Hsp to increase the hepatic functional reserve, and clinical application can be recommended.