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膳食核苷酸对硫代乙酰胺损伤的大鼠肝脏具有细胞保护特性。

Dietary nucleotides have cytoprotective properties in rat liver damaged by thioacetamide.

作者信息

Torres M I, Fernández M I, Gil A, Ríos A

机构信息

Department of Cell Biology, Faculty of Sciences, University of Granada, Spain.

出版信息

Life Sci. 1998;62(1):13-22. doi: 10.1016/s0024-3205(97)01033-3.

DOI:10.1016/s0024-3205(97)01033-3
PMID:9444963
Abstract

Liver cirrhosis has been induced with thioacetamide administered via different routes in rats and other species. The oral intake of thioacetamide causes nodular liver cirrhosis in rats characterized by extensive fibrosis occupying most of the hepatic parenchyma. To characterize the cytological features of cirrhosis induced by thioacetamide, and the degree of recovery obtained with dietary nucleotides, we made a morphometric study of the hepatocytes in rats administered 300 mg/l of thioacetamide for 4 months, and in rats receiving the same hepatotoxic treatment but allowed a 2-weeks recovery period on a nucleotide-free diet or a 250 mg/100 g nucleotide-supplemented diet. Thioacetamide caused to cell damage and affected the ultrastructure of hepatocytes leading to a decrease in cytoplasmic area together with increased nuclear and nucleolar size. Dietary supplementation with nucleotides favoured recovery, restoring the cytoplasmic (TN=491.7+/-9.6 vs TAA=305.1+/-3.7), nuclear (73.6+/-2.8 vs 97.4+/-2.9), and nucleolar area of damaged hepatocytes (5.6+/-0.3 vs 14.0+/-0.9). The injury from thioacetamide intake increased liver collagen, but dietary nucleotides prevented hepatic deposition of this protein. This study supports the hypothesis that dietary supplementation with nucleotides is decisive in ensuring hepatocyte recovery after thioacetamide-induced liver damage, and that dietary nucleotides have antifibrotic properties.

摘要

已通过不同途径给大鼠和其他物种施用硫代乙酰胺诱导肝硬化。口服硫代乙酰胺会导致大鼠出现结节性肝硬化,其特征是广泛的纤维化占据了大部分肝实质。为了表征硫代乙酰胺诱导的肝硬化的细胞学特征以及膳食核苷酸的恢复程度,我们对给予300 mg/l硫代乙酰胺4个月的大鼠以及接受相同肝毒性处理但在无核苷酸饮食或补充250 mg/100 g核苷酸的饮食上有2周恢复期的大鼠的肝细胞进行了形态计量学研究。硫代乙酰胺导致细胞损伤并影响肝细胞的超微结构,导致细胞质面积减少,同时细胞核和核仁大小增加。膳食补充核苷酸有利于恢复,恢复了受损肝细胞的细胞质(TN = 491.7±9.6 vs TAA = 305.1±3.7)、细胞核(73.6±2.8 vs 97.4±2.9)和核仁面积(5.6±0.3 vs 14.0±0.9)。摄入硫代乙酰胺造成的损伤增加了肝脏胶原蛋白,但膳食核苷酸可防止这种蛋白质在肝脏中的沉积。这项研究支持了以下假设:膳食补充核苷酸对于确保硫代乙酰胺诱导的肝损伤后肝细胞的恢复具有决定性作用,并且膳食核苷酸具有抗纤维化特性

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