Minuk G Y, Gauthier T, Gaharie A, Murphy L J
Liver Diseases Research Laboratory, University of Manitoba, Winnipeg, Canada.
Hepatology. 1991 Oct;14(4 Pt 1):685-9. doi: 10.1016/0270-9139(91)90058-4.
Serum and hepatic polyamine concentrations including putrescine, spermidine and spermine were documented at various time intervals after partial hepatectomy in rats treated with GABA (500 micrograms/gm body wt) or isotonic saline. Aside from a transient decrease in spermidine levels, GABA treatment had no effect on serum polyamine concentrations. In the liver, however, GABA treatment markedly attenuated the increase in hepatic putrescine concentrations that occurs after partial hepatectomy such that levels were 64%, 74% and 100% lower than in saline-treated controls on days 1, 2 and 3 after partial hepatectomy (p less than 0.005, p less than 0.01 and p less than 0.05, respectively). Spermidine and spermine concentrations in the liver were not affected by GABA treatment. To determine the mechanism whereby GABA lowers putrescine concentrations in regenerating liver, ornithine decarboxylase messenger RNA and enzyme activity were documented after GABA treatment. Although ornithine decarboxylase messenger RNA levels were similar, ornithine decarboxylase enzyme activity was significantly inhibited 12 hr after partial hepatectomy in GABA-treated rats compared with saline-treated controls. The results of this study indicate that GABA inhibits hepatic putrescine synthesis at a posttranscriptional level in rats after partial hepatectomy. These results could help to explain the impairment in hepatic regenerative activity that occurs in patients with elevated serum GABA concentrations and fulminant hepatic failure.
在接受γ-氨基丁酸（GABA，500微克/克体重）或等渗盐水治疗的大鼠部分肝切除术后的不同时间间隔，记录了血清和肝脏中的多胺浓度，包括腐胺、亚精胺和精胺。除了亚精胺水平短暂下降外，GABA治疗对血清多胺浓度没有影响。然而，在肝脏中，GABA治疗显著减弱了部分肝切除术后肝脏腐胺浓度的升高，以至于在部分肝切除术后第1、2和3天，其水平分别比盐水处理的对照组低64%、74%和100%（p分别小于0.005、p小于0.01和p小于0.05）。GABA治疗对肝脏中的亚精胺和精胺浓度没有影响。为了确定GABA降低再生肝脏中腐胺浓度的机制，在GABA治疗后记录了鸟氨酸脱羧酶信使核糖核酸和酶活性。尽管鸟氨酸脱羧酶信使核糖核酸水平相似，但与盐水处理的对照组相比，GABA治疗的大鼠在部分肝切除术后12小时鸟氨酸脱羧酶活性受到显著抑制。本研究结果表明，GABA在转录后水平抑制部分肝切除术后大鼠肝脏中腐胺的合成。这些结果有助于解释血清GABA浓度升高和暴发性肝衰竭患者肝脏再生活性受损的原因。
