禁食和非禁食大鼠缺血性损伤肝脏中肿瘤坏死因子-α和热休克蛋白基因的表达。供体禁食在预防肝移植后再灌注损伤中的作用。

TNF-alpha and heat-shock protein gene expression in ischemic-injured liver from fasted and non-fasted rats. Role of donor fasting in the prevention of reperfusion injury following liver transplantation.

作者信息

Nishihara M, Sumimoto R, Fukuda Y, Southard J H, Asahara T, Kawaishi H, Dohi K

机构信息

Second Department of Surgery, School of Medicine, Hiroshima University, Japan.

出版信息

Transpl Int. 1998;11 Suppl 1:S417-20. doi: 10.1007/s001470050512.

DOI:10.1007/s001470050512

PMID:9665030

Abstract

We have previously shown that livers from long-term-fasted rats acquire tolerance to warm ischemic injury following transplantation, despite the fact that fasting depletes glycogen and ATP from the liver. The precise mechanism of the protective effect induced by donor fasting, however, is still a matter of controversy. In this experiment we determined heat-shock protein (GRP78) mRNA expression in livers during long-term fasting and TNF-alpha mRNA expression in transplanted livers exposed to warm ischemia. We also measured the concentration of TNF-alpha by ELISA in the ascitic fluid of fed and fasted rats injected intraperitoneally with zymosan to investigate why livers from fasted rats tolerate ischemic injury better. There seemed to be a positive correlation between GRP78 mRNA expression and survival. TNF-alpha secretion into the ascitic fluid of fasted rats was markedly suppressed, and fasting donor animals induced cytoprotective substances, such as GRP78, in the liver. These factors may contribute to the tolerance to ischemic injury produced by donor fasting.

摘要

我们之前已经表明，长期禁食大鼠的肝脏在移植后对热缺血损伤具有耐受性，尽管禁食会耗尽肝脏中的糖原和三磷酸腺苷。然而，供体禁食诱导的保护作用的确切机制仍存在争议。在本实验中，我们测定了长期禁食期间肝脏中热休克蛋白（GRP78）mRNA的表达，以及暴露于热缺血的移植肝脏中肿瘤坏死因子-α（TNF-α）mRNA的表达。我们还通过酶联免疫吸附测定法（ELISA）测量了腹腔注射酵母聚糖的喂食和禁食大鼠腹水中TNF-α的浓度，以研究为什么禁食大鼠的肝脏对缺血损伤的耐受性更好。GRP78 mRNA表达与存活率之间似乎存在正相关。禁食大鼠腹水中TNF-α的分泌明显受到抑制，并且禁食供体动物的肝脏中诱导产生了细胞保护物质，如GRP78。这些因素可能有助于供体禁食产生的缺血损伤耐受性。