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肝毒性药物硫代乙酰胺可诱导大鼠小肠发生生化和组织学改变。

Hepatotoxic agent thioacetamide induces biochemical and histological alterations in rat small intestine.

作者信息

Ortega M A, Torres M I, Fernández M I, Rios A, Sánchez-Pozo A, Gil A

机构信息

Department of Biochemistry and Molecular Biology, University of Granada, Spain.

出版信息

Dig Dis Sci. 1997 Aug;42(8):1715-23. doi: 10.1023/a:1018817600238.

Abstract

We have assessed the effect of the oral ingestion of thioacetamide on small intestine structure and function. Thioacetamide-treated rats showed diminished mucosa weight; protein, DNA, and RNA content; and leucine aminopeptidase activity as compared to controls in both jejunum and ileum. In the jejunum, there was a reduction in the activities of alkaline phosphatase, ATPase, glucose-6-phosphatase, and myeloperoxidase, whereas in the ileum, maltase, lactase, and gamma-glutamyltranspeptidase were reduced. In both jejunum and ileum we found enlarged intercellular spaces, dark epithelial enterocytes, and lymphocyte infiltration. Enterocytes showed lobulated nuclei, deranged mitochondria with loss of their cristae, dilated rough endoplasmic reticulum containing dense material, and vesiculation of the smooth endoplasmic reticulum and the Golgi apparatus. Smooth muscle cells of the intestine exhibited ultrastructural alterations. These findings indicate that chronic oral intake of thioacetamide mimics not only hepatic alterations but also small intestine alterations normally associated with human cirrhosis.

摘要

我们评估了口服硫代乙酰胺对小肠结构和功能的影响。与对照组相比,硫代乙酰胺处理的大鼠空肠和回肠的黏膜重量、蛋白质、DNA和RNA含量以及亮氨酸氨肽酶活性均降低。在空肠中,碱性磷酸酶、ATP酶、葡萄糖-6-磷酸酶和髓过氧化物酶的活性降低,而在回肠中,麦芽糖酶、乳糖酶和γ-谷氨酰转肽酶降低。在空肠和回肠中,我们都发现细胞间隙增大、上皮肠细胞变黑以及淋巴细胞浸润。肠细胞显示核呈分叶状,线粒体排列紊乱,嵴消失,粗面内质网扩张并含有致密物质,滑面内质网和高尔基体出现囊泡化。肠道平滑肌细胞表现出超微结构改变。这些发现表明,长期口服硫代乙酰胺不仅会模拟肝脏改变,还会模拟通常与人类肝硬化相关的小肠改变。

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