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

我们已经发现，肝脏血流中氧气含量的增加改善了肝功能。肝细胞中的热休克蛋白(HSP)与DNA损伤密切相关，其改善依赖于ATP代谢，提示通过适当的方法诱导肝细胞HSP可有效地保护肝脏免受手术损伤。在此基础上，我们制定了通过肝脏氧合来提高肝切除术安全性的计划，并提前利用高温诱导肝细胞HSP。虽然已经进行了许多关于肝储备功能的研究，但其结果被用于区分手术后潜在的肝功能衰竭患者，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等内在因素来增加肝脏的功能储备，以承受手术创伤。HSP在肝脏中的含量和定位随着肝功能不全程度的不同而变化。HSP73是在43度(C)的水中全身浸泡在肝细胞中诱导的，其位置位于胞核和胞浆之间。免疫印迹法检测HSP体积的诱导取决于热暴露的持续时间和时间。在提前诱导HSP的大鼠中，肝缺血、内毒素注射和硫代乙酰胺所致的肝损伤可以得到保护。肝静脉回流对肝细胞的缺血损伤有保护作用，可支持肝脏氧合作用的意义，并可提前诱导HSP增加肝脏储备功能，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.