外源多胺对大鼠再生肝细胞鸟氨酸脱羧酶基因转录的调节

REGULATION OF EXOGENOUS POLYAMINES ON ORNITHINE DECARBOXYLASE GENE TRANSCRIPTION IN REGENERATING RAT HEPATOCYTES

目的研究天然多胺(腐胺、精脒和精胺)对大鼠再生肝细胞鸟氨酸脱羧酶(ODC)基因转录的调节,探讨多胺在肝再生中的作用。方法大鼠部分肝切除术诱导再生肝,采用原位杂交技术分析ODC mRNA的表达量,外源多胺(溶于0.9%NaCl)的处理用皮下注射法。结果外源多胺处理后,再生肝ODC mRNA水平的变化趋势与对照组相似,但不同种类、剂量的多胺,结果差异明显。在所观察到的整个肝再生期间,高剂量腐胺(20mg/kg体重)处理组mRNA水平始终低于对照组,特别在部分肝切除后2、4和10h与对照组相比具有显著性差异(P<0.05);低剂量(0.02mg/kg体重)的腐胺处理组,只在4h和12h显著高于对照组。高剂量精脒(0.15mg/kg体重)处理组的ODC mRNA水平始终低于对照组(在10h例外);而低剂量(0.03 mg/kg体重)处理组则不同,ODC mRNA水平表现出先抑制(在2h)后促进(在4h和6h)的特点。精胺的作用与精脒相似。结论不同浓度的多胺(主要是精脒和精胺)对大鼠再生肝细胞ODC基因转录存在着反馈调节作用。

Objective To study the regulation of natural polyamines （putrescine, spermidine and spermine） on omithine decarbexylase gene transcription in regenerating rat hepatocytes and to assess the roles of polyamines in liver regeneration. Methods Rat regenerating liver was induced by surgical partial hepatectomy （PH）. The expressive levels of ODC mRNA in regenerating liver were measured by in situ hybridization analysis. Exogenous polyamines （dissolved in 0.9% NaCl） were administered subcutaneously to adult male Sprague-Dawley rats. Results ODC mRNA expression was always lower in high dose （20 mg/kg body weight） putrescine-treated rats compared with that in control rats during the observed regeneration, especially at the 2 nd, 4 th and 10 th hours（ P 〈 0.05） after PH; but it was higher in low dose （0.02 mg/kg body weight） putrescine-treated group compared with that in control group only at the 4 th and 12 th hours（ P 〈 0.05） post-PH. The mRNA levels in 0.15 mg/kg spermidine-treated group were below the control group in the whole experiment except at the 10 th hour post-PH ; however, 0.03 mg/kg spermidine treatment, first statistically decreasing the mRNA level in the 2 hours after PH, promoted the increase in ODC mRNA at the 4 th and 6 th hours after PH respectively. The effect of spermine on ODC mRNA expression was similar to that of spermidine. Conclusion Polyamines （especially spermine and spermine） of different concentrations are involved in feedback regulating ODC gene transcription in rat regenerating hepatocytes.