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

通过提前诱导心休克蛋白和肝氧合减少肝手术后的肝损伤

• 批准号: 06454377
• 负责人: KOYAMA Kenji
• 金额: $ 4.74万
• 依托单位: AKITA UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (B)
• 财政年份: 1994
• 资助国家: 日本
• 起止时间: 1994 至 1995
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-06454377/
• 关键词: Hepatic injury; Heat Shock Protein; DNA injury; NICK; Ischemia and reperfusion-injury; Heat Shock protein; 近赤外分光々光計; 阻血再潅流障害

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.

我们已经发现，肝血流中氧含量的增加可以改善肝功能。另据报道，肝细胞中的热休克蛋白（Hsp）与DNA损伤及其依赖于ATP代谢的改善密切相关，这表明通过某种合适的方法诱导肝细胞中的Hsp可有助于保护肝脏免受手术损伤。在此基础上，我们制定了通过肝氧合提高肝硬化肝切除术的安全性的计划。 并利用高温促进肝细胞Hsp的诱导。尽管已经进行了许多关于肝功能储备的研究，但这些结果被用于区分手术后潜在肝功能衰竭的患者，这些患者应被排除在肝切除术之外。针对此类患者，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。在本次大鼠实验中，获得了以下结果。1)。肝脏中Hsp的含量和定位根据肝功能障碍的程度而变化。2)。通过将整个细胞浸入43℃的水中，在肝细胞中诱导Hsp73，并改变其在细胞核和细胞质之间的位置。3)。根据热暴露的持续时间和时间，通过免疫印迹测量的 Hsp 体积诱导变化。4)。提前诱导Hsp的大鼠，可以保护由肝缺血、内毒素输注和硫代乙酰胺引起的肝损伤。5)。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Hsp以增加肝功能储备的重要性，值得临床应用。

项目成果

Andoh H,Koyama k et al.: "Heart shock protein 70 in rat liver with necrosis and regeneration induced by thioacetamide." J Gastroenterology. 29. 293-298 (1994)

Andoh H、Koyama k 等人：“硫代乙酰胺诱导大鼠肝脏坏死和再生时的心休克蛋白 70”。

Andoh H,Koyama K et al.: "Heat shock protein 70 in rat liver regeneration after hepatectomy." International Hepatology Communication. 2. 191-196 (1994)

Andoh H、Koyama K 等人：“热休克蛋白 70 在肝切除术后大鼠肝脏再生中的作用。”

Andoh H: "Heat shock protein 70 in rat liver regeneration after hepatectomy" International Hepatology Communication. 2. 191-196 (1994)

Andoh H：“热休克蛋白 70 在肝切除术后大鼠肝脏再生中的作用”国际肝脏病学通讯。

Andoh H: "Heat shock protein 70 in rat liver with necrosis and regeneration induced by thioacetamide" J Gastroenterology. 29. 293-298 (1994)

Andoh H：“硫代乙酰胺诱导大鼠肝脏坏死和再生的热休克蛋白 70”J Gastroenterology。