Adaptive Response of Growing Rat Small Intestine to Acute AdriamycinTM Injury

Adaptive Response of Growing Rat Small Intestine to Acute AdriamycinTM Injury
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生长大鼠小肠对阿霉素急性损伤的适应性反应

DOI:
10.1097/00005176-198302010-00019
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发表时间:
1983
期刊:
Journal of Pediatric Gastroenterology and Nutrition - JPGN
影响因子:
--
通讯作者:
P. Maldague
P. Maldague
中科院分区:
--
文献类型:
--
作者:
J. Buts;R. Meyer;M. Craynest;P. Maldague

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本文观察了25日龄大鼠十二指肠、空肠和回肠对阿霉素(ADR)的反应。单次注射ADR导致每厘米长度的粘膜DNA和蔗糖酶活性降低,与给药剂量(2、5和8 mg/kg)成比例。2 mg/kg的ADR对体重、肠道长度、上皮结构或每单位长度的粘膜蛋白含量无显著影响。小肠形态学改变主要发生在近端,包括绒毛萎缩和绒毛及隐窝细胞的退行性改变。5 mg ADR/kg单次给药急性影响肠道。在48和96小时的变化的特点是显着减少粘膜重量,每厘米DNA,蔗糖酶活性,绒毛缩短。在144 h时,ADR处理的肠进入高度增殖状态,并显示绒毛高度、粘膜重量和每厘米DNA增加。虽然在144和192 h观察到绒毛增生,但粘膜重量和DNA浓度未超过对照组的相应水平。在活跃的上皮细胞增殖期间,蔗糖酶活性仍然受到抑制。我们的结论是,在生长的大鼠:(a)ADR的急性肠损伤是短暂的,剂量依赖性,并在近端小肠占主导地位:(B)肠粘膜反应的细胞毒性损伤的过度增殖的不成熟的肠细胞;和(c)ADR的增生反应仅限于粘膜上皮。
The response of the intestinal mucosa to AdriamycinTM (ADR) was studied in the duodenum, jejunum, and ileum of 25-day-old rats. A single injection of ADR resulted in decreases in mucosal DNA per centimeter of length and in sucrase activity, which were proportional to the doses given (2, 5, and 8 mg/kg). ADR at 2 mg/kg had no significant effect on body weight, gut length, epithelial structure, or mucosal protein content per unit length. The morphological modifications occurred mostly in the proximal intestine and consisted of villous atrophy and degenerative changes of villus and crypt cells. A single dose of 5 mg ADR/kg acutely affected the gut. At 48 and 96 h the changes were characterized by marked decreases in mucosal weight, DNA per centimeter, sucrase activity, and villous shortening. At 144 h, the ADR-treated intestine entered a highly proliferative state and showed increased villous height, mucosal weight, and DNA per centimeter. Although villous hyperplasia was observed at 144 and 192 h, the mucosal weight and DNA concentrations did not exceed the corresponding levels in the control. During the period of active epithelial proliferation, sucrase activity remained depressed. We conclude that in the growing rat: (a) the acute intestinal injury of ADR is short-lived, dose dependent, and predominates in the proximal small intestine: (b) the enteric mucosa reacts to cytotoxic injury by excessive proliferation of immature enterocytes; and (c) the hyperplastic response to ADR is confined to the mucosal epithelium.