Beyer H S, Ellefson M, Sherman R, Zieve L
Department of Medicine, Hennepin County Medical Center, Minneapolis, MN 55415.
J Lab Clin Med. 1992 Jan;119(1):38-47.
Aging decreases rat liver regeneration. We (1) compared the expression of ornithine decarboxylase (ODC), a critical enzyme for liver regeneration, and polyamine levels in regenerating liver of 6-week-old and 1-year-old rats and (2) evaluated the effect of exogenous putrescine supplementation on liver regeneration in 1-year-old rats. ODC messenger ribonucleic acid (mRNA) transcript sizes were the same in rats of both ages. ODC mRNA content and enzyme activity were higher in the younger rats; however, magnitudes of increase after partial hepatectomy were greater in the older rats. From peak levels, the rate of decline of the mRNA was slower in the older rats, but enzyme activity declined at the same rate in both ages. ODC apoenzyme content was significantly less in normal liver tissue from 1-year-old rats, but there was little change after partial hepatectomy in rats of either age. No change in ODC transcriptional activity was found. Hepatic putrescine levels were lower in 48 hours regenerating liver tissue from 1-year-old rats. To determine whether supplemental putrescine would increase liver regeneration in 1-year-old rats, putrescine (600 mumol/kg IP every 4 hours) was administered beginning 4 days before or at the time of partial hepatectomy. This raised polyamine levels and decreased ODC activity significantly, but there was no change in regenerating liver weight, total DNA and RNA content, and tritiated thymidine incorporation at 48 hours. These results indicate that ODC expression is different and polyamine levels are lower in 1-year-old rats than in 6-week-old rats. However, putrescine supplementation that is sufficient to decrease ODC activity has no apparent effect on regeneration.
衰老会降低大鼠肝脏的再生能力。我们（1）比较了鸟氨酸脱羧酶（ODC，肝脏再生的关键酶）的表达以及6周龄和1岁大鼠再生肝脏中的多胺水平，（2）评估了外源性补充腐胺对1岁大鼠肝脏再生的影响。两个年龄段大鼠的ODC信使核糖核酸（mRNA）转录本大小相同。年轻大鼠的ODC mRNA含量和酶活性更高；然而，部分肝切除术后老年大鼠的增加幅度更大。从峰值水平来看，老年大鼠mRNA的下降速率较慢，但两个年龄段的酶活性下降速率相同。1岁大鼠正常肝组织中的ODC脱辅基酶含量明显较低，但两个年龄段大鼠部分肝切除术后变化不大。未发现ODC转录活性有变化。1岁大鼠48小时再生肝组织中的肝腐胺水平较低。为了确定补充腐胺是否会增加1岁大鼠的肝脏再生能力，在部分肝切除术前4天或手术时开始给予腐胺（每4小时腹腔注射600 μmol/kg）。这显著提高了多胺水平并降低了ODC活性，但48小时时再生肝脏重量、总DNA和RNA含量以及氚标记胸腺嘧啶核苷掺入量均无变化。这些结果表明，1岁大鼠的ODC表达不同，多胺水平低于6周龄大鼠。然而，足以降低ODC活性的腐胺补充对再生没有明显影响。
