Imano M
Department of Public Health, Osaka City University Medical School, Japan.
Nihon Arukoru Yakubutsu Igakkai Zasshi. 1998 Jun;33(3):241-51.
We studied the effects of glucagon and insulin (GI) administration on the inhibition of liver regeneration by acute ethanol treatment after partial hepatectomy (PH) in rats. When ethanol was given 1 hour before PH at 3 gm/kg body wt., [3H] thymidine incorporation into the hepatic DNA 24 hr after PH was significantly inhibited, but it was completely reversed by GI treatment. Although hepatic ornithine decarboxylase (ODC) activity in the ethanol-treated group 4 hr after PH was significantly inhibited, it was completely reversed by GI treatment. The putrescine (PUT) level in the liver 4 hr after PH was decreased by ethanol, but it was increased by GI treatment. At 12 hr after PH, ODC activity was not inhibited and PUT level in the liver was not decreased by ethanol. The levels of spermidine and spermine in the liver 4 hr after PH were unaffected either by ethanol or by GI treatment. Spermidine/spermine-N1 acetyltransferase activity in the liver 4 hr after PH was showed a tendency to increase by ethanol but it was decreased by GI treatment. Difluoromethylornithine, a specific inhibitor of ODC, decreased the level of PUT in the liver, and inhibited [3H] thymidine incorporation. The intraperitotneal administration of PUT significantly increased [3H] thymidine incorporation. The increase in ODC mRNA caused by pH was inhibited by ethanol, but it was completely reversed by GI treatment. SAT mRNA was affected neither by ethanol ner GI treatment. These results suggested that GI treatment was effective on the inhibition of liver regeneration by acute ethanol treatment, and activation of liver regeneration by GI treatment is closely related with ODC induction at the level of transcription.
我们研究了胰高血糖素和胰岛素(GI)给药对大鼠部分肝切除(PH)后急性乙醇处理抑制肝再生的影响。当在PH前1小时以3克/千克体重给予乙醇时,PH后24小时肝DNA中[3H]胸苷掺入显著受到抑制,但GI处理可使其完全逆转。尽管PH后4小时乙醇处理组的肝鸟氨酸脱羧酶(ODC)活性显著受到抑制,但GI处理可使其完全逆转。PH后4小时肝中的腐胺(PUT)水平因乙醇而降低,但GI处理使其升高。PH后12小时,ODC活性未受抑制,肝中的PUT水平也未因乙醇而降低。PH后4小时肝中的亚精胺和精胺水平不受乙醇或GI处理的影响。PH后4小时肝中的亚精胺/精胺-N1乙酰转移酶活性有因乙醇而升高的趋势,但GI处理使其降低。ODC的特异性抑制剂二氟甲基鸟氨酸降低了肝中PUT的水平,并抑制了[3H]胸苷掺入。腹腔注射PUT显著增加了[3H]胸苷掺入。由pH引起的ODC mRNA增加受到乙醇抑制,但GI处理使其完全逆转。SAT mRNA既不受乙醇也不受GI处理的影响。这些结果表明,GI处理对急性乙醇处理抑制肝再生有效,且GI处理激活肝再生与转录水平上的ODC诱导密切相关。