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出生后大鼠胰腺发育过程中IGF-I mRNA表达下调,胰腺次全切除和急性胰腺炎后表达上调。

Downregulation of IGF-I mRNA expression during postnatal pancreatic development and overexpression after subtotal pancreatectomy and acute pancreatitis in the rat pancreas.

作者信息

Calvo E L, Bernatchez G, Pelletier G, Iovanna J L, Morisset J

机构信息

Département de Médecine, Faculté de Médicine, Université de Sherbrooke, Quebec, Canada.

出版信息

J Mol Endocrinol. 1997 Jun;18(3):233-42. doi: 10.1677/jme.0.0180233.

DOI:10.1677/jme.0.0180233
PMID:9195477
Abstract

Insulin-like growth factors (IGFs) are important peptides involved in the regulation of cell growth and differentiation in many tissues. The ontogeny of IGF-I was examined in pancreata from 19-day rat fetuses, newborns and 5-, 11-, 26- and 70-day-old rats. For the regeneration studies two models were used: (i) 90% pancreatectomy was carried out and the rats were killed at 1, 2, 3 and 6 days after resection; (ii) acute pancreatitis was induced with caerulein (12 micrograms/body weight three times a day every 8 h for 2 days) and the rats were killed at 1, 2, 5, 7 and 9 days after the first injection. Total RNA was extracted by the guanidinium isothiocyanate method and Northern blots were performed using total RNA and labeled cRNA probes. Abundance of the different mRNA transcripts was estimated by densitometric scanning and normalized to the abundance of 18 S rRNA for each time point. Northern blot analysis during ontogeny showed four (0.8-1.2, 1.9, 4.7 and 7.5 kb) major transcripts in the rat pancreas and liver. Total IGF-I mRNA was 40-fold higher in the adult liver than in the adult pancreas. Moreover, in the liver, IGF-I mRNA levels were higher in the adult than in the fetus, whereas in the pancreas, the highest levels were observed around birth. During the first 3 days after pancreatectomy, a peak of maximal expression was observed after the second day. Densitometric analysis of each IGF-I mRNA species showed concomitant increases in all transcripts. After 6 days, all transcripts had returned to near-control values. IGF-I mRNA expression 2 days after pancreatectomy was 3.5-fold higher than in the newborn. During the first 2 days of acute pancreatitis induction, overexpression of IGF-I mRNA was observed. However, soon after the second day of caerulein treatment, the 7.5 kb transcripts remained elevated whereas those of the others regressed toward control values. Our results show that IGF-I mRNA is overexpressed in both models of pancreatic regeneration but downregulated in the normal adult pancreas.

摘要

胰岛素样生长因子(IGFs)是参与许多组织中细胞生长和分化调节的重要肽类。研究了19天龄大鼠胎儿、新生大鼠以及5日龄、11日龄、26日龄和70日龄大鼠胰腺中IGF-I的个体发生情况。对于再生研究,使用了两种模型:(i)进行90%胰腺切除术,并在切除后1天、2天、3天和6天处死大鼠;(ii)用蛙皮素诱导急性胰腺炎(每8小时一次,每次12微克/体重,共2天),并在首次注射后1天、2天、5天、7天和9天处死大鼠。采用异硫氰酸胍法提取总RNA,并用总RNA和标记的cRNA探针进行Northern印迹分析。通过光密度扫描估计不同mRNA转录本的丰度,并针对每个时间点将其标准化为18S rRNA的丰度。个体发生过程中的Northern印迹分析显示,大鼠胰腺和肝脏中有四种(0.8 - 1.2 kb、1.9 kb、4.7 kb和7.5 kb)主要转录本。成年肝脏中的总IGF-I mRNA比成年胰腺中的高40倍。此外,在肝脏中,成年期的IGF-I mRNA水平高于胎儿期,而在胰腺中,出生前后观察到最高水平。胰腺切除术后的前3天,在第二天后观察到最大表达峰值。对每种IGF-I mRNA种类的光密度分析显示所有转录本均伴随增加。6天后,所有转录本均恢复到接近对照值。胰腺切除术后2天的IGF-I mRNA表达比新生大鼠高3.5倍。在急性胰腺炎诱导的前2天,观察到IGF-I mRNA的过表达。然而,在蛙皮素治疗第二天后不久,7.5 kb的转录本仍然升高,而其他转录本则回归到对照值。我们的结果表明,IGF-I mRNA在两种胰腺再生模型中均过表达,但在正常成年胰腺中下调。

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