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可以改善肝功能。肝细胞热休克蛋白（Hsp）与dninjury有密切关系，其改善依赖于ATP代谢，提示通过适当的方法诱导肝细胞热休克蛋白（Hsp）对肝脏损伤有保护作用。在此基础上，我们计划通过肝氧合提高肝硬化肝癌切除术的安全性，并利用热疗提前诱导肝细胞热休克。虽然有很多关于肝功能储备的研究，但这些研究结果被用来区分术后可能出现肝功能衰竭的患者，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的氧浓度或诱导细胞内热休克蛋白等内在因素来增加肝脏承受手术损伤的功能储备。本实验以大鼠为实验对象，得到如下结果：1)。肝内热休克蛋白的含量和定位随肝功能障碍程度的变化而变化(2)。将Hsp73全身浸泡在43度(C)的水中，在肝细胞中诱导，并改变其在细胞核和细胞质之间的位置3)。免疫印迹法测定的热休克蛋白诱导量随热暴露时间的长短而变化。热休克提前诱导大鼠肝缺血、内毒素输注和硫代乙酰胺对肝损伤均有保护作用。肝静脉回流似乎可以保护肝细胞免受流入阻塞引起的缺血性损伤。这些结果可以支持肝氧合和提前诱导热休克蛋白对增加肝功能储备的意义，推荐临床应用。

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.