Ito Koji, Ozasa Hisashi, Noda Yumi, Koike Yuichi, Arii Shigeki, Horikawa Saburo
Division of Pathophysiology, Medical Research Institute, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan.
Clin Nutr. 2008 Oct;27(5):773-80. doi: 10.1016/j.clnu.2008.06.012. Epub 2008 Aug 8.
BACKGROUND & AIMS: Liver regeneration after partial hepatectomy or transplantation is a critical problem to affect prognosis. Ischemia/reperfusion (I/R) is an unavoidable process during liver resection or transplantation. The aim of this study was to investigate the effect of glycine on the regeneration of the remnant liver with I/R injury after partial hepatectomy.
Partially hepatectomized rat with liver I/R injury was prepared by a two-thirds partial hepatectomy following 30 min of total hepatic ischemia. Glycine (5% in water) was orally administered to rats for 3 days as drinking water before the surgery.
Mortality rate in partially hepatectomized rats with severe hepatic I/R injury was so high compared to that in the rats with partial hepatectomy alone. However, when glycine was given to the partially hepatectomized rats with hepatic I/R injury, the survival rate, the recovery rate of the remnant liver weight, and the liver injury were obviously improved. On the other hand, when glycine-treated rats underwent partial hepatectomy without hepatic I/R, the recovery rate of the remnant liver weight was decreased as compared with that of the rats with partial hepatectomy alone. In these settings, glycine administration prevented the elevation of serum TNF-alpha levels and liver TNF-alpha mRNA expression.
Glycine improved the regeneration of the remnant liver with severe I/R injury after partial hepatectomy. This improvement may be at least partly due to the amelioration of the hepatic I/R injury by glycine. Glycine seems to be clinically beneficial to the prognosis of patients with liver resection.
部分肝切除或肝移植后的肝脏再生是影响预后的关键问题。缺血/再灌注(I/R)是肝切除或肝移植过程中不可避免的环节。本研究旨在探讨甘氨酸对部分肝切除术后伴有I/R损伤的残余肝脏再生的影响。
通过三分之二部分肝切除并在全肝缺血30分钟后制备伴有肝脏I/R损伤的部分肝切除大鼠。在手术前,将甘氨酸(5%溶于水)作为饮用水口服给予大鼠3天。
与单纯部分肝切除的大鼠相比,伴有严重肝脏I/R损伤的部分肝切除大鼠的死亡率很高。然而,当给伴有肝脏I/R损伤的部分肝切除大鼠给予甘氨酸时,存活率、残余肝脏重量的恢复率以及肝损伤均明显改善。另一方面,当经甘氨酸处理的大鼠在无肝脏I/R的情况下接受部分肝切除时,与单纯部分肝切除的大鼠相比,残余肝脏重量的恢复率降低。在这些情况下,给予甘氨酸可防止血清TNF-α水平升高和肝脏TNF-α mRNA表达增加。
甘氨酸改善了部分肝切除术后伴有严重I/R损伤的残余肝脏的再生。这种改善可能至少部分归因于甘氨酸对肝脏I/R损伤的改善。甘氨酸似乎对肝切除患者的预后具有临床益处。