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褪黑素与X线照射诱导的白化大鼠急性放射性肠炎:一种动物模型

Melatonin and roentgen irradiation-induced acute radiation enteritis in Albino rats: an animal model.

作者信息

Hussein Mahmoud R, Abu-Dief Eman E, Kamel Esam, Abou El-Ghait Amal T, Abdulwahed Saad Rezk, Ahmad Mohamed H

机构信息

Department of Pathology, Faculty of Medicine, Assuit University, Assuit, Egypt.

出版信息

Cell Biol Int. 2008 Nov;32(11):1353-61. doi: 10.1016/j.cellbi.2008.08.001. Epub 2008 Aug 13.

Abstract

BACKGROUND

Roentgen irradiation can affect normal cells, especially the rapidly growing ones such as the mucosal epithelial cells of the small intestine. The small intestine is the most radiosensitive gastrointestinal organ and patients receiving radiotherapy directed to the abdomen or pelvis may develop radiation enteritis. Although roentgen rays are widely used for both imaging and therapeutic purposes, our knowledge about the morphological changes associated with radiation enteritis is lacking.

HYPOTHESIS

This study tries to tests the hypothesis that "the intake of melatonin can minimize the morphological features of cell damage associated with radiation enteritis".

OBJECTIVES AND METHODS

We performed this investigation to test our hypothesis and to examine the possible radioprotective effects of melatonin in acute radiation enteritis. To achieve these goals, an animal model consisting of 60 Albino rats was established. The animals were divided into five groups: Group 1, non-irradiated; Group 2, X-ray irradiated (X-ray irradiation, 8 Grays); Group 3, X-ray irradiated-pretreated with solvent (ethanol and phosphate buffered saline); Group 4, non-irradiated-group treated with melatonin, and Group 5, X-ray irradiated-pretreated with melatonin. The small intestines were evaluated for gross (macroscopic), histological, morphometric (light microscopy), and ultrastructural changes (transmission electron microscopy).

RESULTS

We found morphological variations among the non-irradiated-group, X-ray irradiated-group and X-ray irradiated-intestines of the animals pretreated with melatonin. The development of acute radiation enteritis in X-ray irradiated-group (Groups 2 and 3) was associated with symptoms of enteritis (diarrhea and abdominal distention) and histological features of mucosal injury (mucosal ulceration, necrosis of the epithelial cells). There was a significant reduction of the morphometric parameters (villous count, villous height, crypt height and villous/crypt height ratio). Moreover, the ultrastructural features of cell damage were evident including: apoptosis, lack of parallel arrangement of the microvilli, loss of the covering glycocalyx, desquamation of the microvilli, vacuolation of the apical parts of the cells, dilatation of the rough endoplasmic reticulum, and damage of the mitochondrial cristae. In the non-irradiated-group and in X-ray irradiated-intestines of the animals pretreated with melatonin (Group 5), these changes were absent and the intestinal mucosal structure was preserved.

CONCLUSION

Administration of melatonin prior to irradiation can protect the intestine against X-rays destructive effects, i.e. radiation enteritis. The clinical applications of these observations await further studies.

摘要

背景

X线照射可影响正常细胞,尤其是快速生长的细胞,如小肠黏膜上皮细胞。小肠是胃肠道中对辐射最敏感的器官,接受腹部或盆腔放疗的患者可能会发生放射性肠炎。尽管X线广泛应用于成像和治疗目的,但我们对与放射性肠炎相关的形态学变化了解不足。

假说

本研究试图验证“摄入褪黑素可使与放射性肠炎相关的细胞损伤形态特征最小化”这一假说。

目的和方法

我们进行这项研究以验证我们的假说,并研究褪黑素在急性放射性肠炎中的可能放射保护作用。为实现这些目标,建立了一个由60只白化大鼠组成的动物模型。动物被分为五组:第1组,未照射;第2组,X线照射(X线照射,8格雷);第3组,X线照射-用溶剂(乙醇和磷酸盐缓冲盐水)预处理;第4组,未照射-用褪黑素处理,第5组,X线照射-用褪黑素预处理。对小肠进行大体(宏观)、组织学、形态计量学(光学显微镜)和超微结构变化(透射电子显微镜)评估。

结果

我们在未照射组、X线照射组和用褪黑素预处理的动物的X线照射小肠中发现了形态学差异。X线照射组(第2组和第3组)急性放射性肠炎的发生与肠炎症状(腹泻和腹胀)以及黏膜损伤的组织学特征(黏膜溃疡、上皮细胞坏死)相关。形态计量学参数(绒毛计数、绒毛高度、隐窝高度和绒毛/隐窝高度比)显著降低。此外,细胞损伤的超微结构特征明显,包括:细胞凋亡、微绒毛平行排列缺失、覆盖糖萼丧失、微绒毛脱落、细胞顶端空泡化、粗面内质网扩张和线粒体嵴损伤。在未照射组和用褪黑素预处理的动物的X线照射小肠(第5组)中,这些变化不存在,肠黏膜结构得以保留。

结论

照射前给予褪黑素可保护肠道免受X线的破坏作用,即放射性肠炎。这些观察结果的临床应用有待进一步研究。

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