Changes in Function of Hepatocyte Tight Junctions and Deal with Endotoxin by Hepatocytes after Hepatic Resection

肝切除后肝细胞紧密连接功能的变化及肝细胞处理内毒素的作用

• 批准号: 11671206
• 负责人: SATO Tsutomu
• 金额: $ 2.18万
• 依托单位: Akita University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11671206/
• 关键词: shear stress; portal venous pressure; prostaglandin E_1; tight junction; liver resection; タイト結合; 肝再生; 門脈圧

[Backgrounds and Aims]It is not known how shear stress onto the hepatic sinusoids influence liver function and regeneration after hepatic resection. Changes in functions of tight junction between hepatocytes were investigated in terms of shear stress represented by portal pressure.[Results]1) After 70% partial hepatectomy in rats, function of tight junction decreased until 7 days after hepatectomy. The function did not improve solely by portal decompression, which was achieved by previous splenic transposition to make portosystemic collaterals. However, the function of tight junction improved by prostaglandin E_1 (PGE_1) infusion.2) To avoid portal hypertension after hepatic resection, portal vein was embolized prior to hepatic resection in pigs. It was clarified that 7 days (after embolization) is enough to accomplish this aim. PGE_1 infusion via the superior mesenteric artery (SMA), which increase portal blood flow without increasing portal pressure, reduced injury to hepatocytes and sinusoidal lining cells after hepatic resection.3) In cases of major hepatic resection, PGE_1 infusion via SMA was performed. Portal blood flow, measured by Doppler US, markedly increased and oxygen saturation of hepatic venous blood also increased. This method was also useful in the treatment of postoperative liver failure.[Conclusion]After hepatic resection, function of tight junction deteriorated in relation to shear stress (portal pressure). To control shear stress after hepatic resection is effective to reduce injury following hepatic resection. PGE_1 infusion via SMA and preoperative portal embolization are both useful.

[背景与目的]肝窦切应力对肝切除术后肝功能和肝再生的影响尚不清楚。以门静脉压力为代表的切应力，研究肝细胞间紧密连接功能的变化。[结果]1）大鼠70%肝部分切除后，紧密连接功能下降，直至术后7天。单纯通过门静脉减压并不能改善功能，而门静脉减压是通过先前的脾移位形成门体侧支循环来实现的。2）为避免肝切除术后门静脉高压症的发生，在猪肝切除前行门静脉栓塞。澄清了7天（栓塞后）足以实现这一目标。经上级肠系膜动脉（SMA）灌注前列腺素E_1，可增加门静脉血流量而不增加门静脉压力，减少肝切除术后肝细胞和肝窦衬里细胞的损伤。多普勒超声测量的门静脉血流量明显增加，肝静脉血氧饱和度也增加。这种方法也适用于术后肝功能衰竭的治疗。[结论]肝切除术后，紧密连接功能恶化，其程度与切应力（门静脉压力）有关。控制切应力是减少肝切除术后损伤的有效措施。SMA灌注PGE_1和术前门静脉栓塞均有效。

项目成果

Sato T, Kato T, Kurokawa T, Yasui O, Miyazawa H, Asanuma Y, Koyama K: "Continuous infusion of prostaglandin E_1 via the superior mesenteric artery can prevent hepatic injury through passive portal oxygenation in hepatic artery interruption."Liver. 20. 179

Sato T、Kato T、Kurokawa T、Yasui O、Miyazawa H、Asanuma Y、Koyama K：“通过肠系膜上动脉持续输注前列腺素 E_1 可以通过肝动脉中断时的被动门静脉氧合来预防肝损伤。”肝脏。

Sato T, et al.: "Prostaglandin E_1 continuous hepatic arterial infusion in the treatment of postoperative acute liver failure"Digestive Surgery. 17. 234-240 (2000)

Sato T等：“前列腺素E_1持续肝动脉灌注治疗术后急性肝功能衰竭”消化外科。

Sato T, Kato T, Kurokawa T, Yasui O, Nanjo H, Asanuma Y, Koyama K: "Alteration of portal blood by continuous PGE_1 infusion via the superior mesenteric artery after hepatic artery interruption."Surgical Forum. 50. 1-2 (1999)

Sato T、Kato T、Kurokawa T、Yasui O、Nanjo H、Asanuma Y、Koyama K：“肝动脉中断后，通过肠系膜上动脉连续输注 PGE_1 来改变门静脉血。”外科论坛。

Sato T, et al.: "Efficacy of hepatic arterial infusion of prostaglandin E_1 in the treatment of postoperative acute liver failure"Hepatogastroenterology. 47. 846-850 (2000)

Sato T等：“肝动脉灌注前列腺素E_1治疗术后急性肝功能衰竭的疗效”肝胃肠病学。

Sato T, et al.: "Alteration of portal blood by continuous PGE_1 infusion via the superior mesenteric artery after hepatic artery interruption"Surgical Forum. 50. 1-2 (1999)

Sato T 等人：“肝动脉中断后，通过肠系膜上动脉连续输注 PGE_1 来改变门静脉血”外科论坛。