Parise E R, Chehter L, Nogueira M D, Leite-Mor M M, Tersariol I L, Michelacci Y M, Nader H B
Gastroenterology Section, Escola Paulista de Medicina, São Paulo, Brazil.
J Lab Clin Med. 1992 Jun;119(6):676-81.
We have investigated the effects of nontoxic doses of vitamin A on the hepatic contents of collagen and sulfated glycosaminoglycans (SGAGs) in rats chronically treated with CCl4. When the animals were treated with this retinoid before the intoxication with CCl4, liver collagen level was significantly reduced as compared with that in rats that received only CCl4 (3.31 +/- 0.40 vs 5.00 +/- 0.61 mg/gm wet liver, mean +/- SD, respectively), although no significant differences were found for the relative proportion of type III collagen related to type I collagen. The absolute increment in the total amount of liver SGAG in the vitamin A--pretreated group was followed by a more important increase in the concentration of dermatan sulfate as compared with the CCl4 group (dermatan sulfate-to-heparan sulfate ratio: 1.15 for the CCl4 group vs 1.70 for the vitamin A--pretreated group). A significant proportion of the dermatan sulfate from this last group was of higher molecular weight when compared with the dermatan sulfate found in the liver of rats that received only CCl4. Our results indicate that the pretreatment with vitamin A modifies hepatic collagen and SGAG deposition and can inhibit or delay the development of liver cirrhosis in rats chronically treated with CCl4. We speculate that this effect could be due to the changes in the fat-storing (Ito) cells phenotype induced by vitamin A.
我们研究了无毒剂量的维生素A对长期用四氯化碳处理的大鼠肝脏中胶原蛋白和硫酸化糖胺聚糖(SGAGs)含量的影响。在用四氯化碳中毒之前用这种类维生素A处理动物时,与仅接受四氯化碳处理的大鼠相比,肝脏胶原蛋白水平显著降低(分别为3.31±0.40与5.00±0.61mg/g湿肝,均值±标准差),尽管在III型胶原蛋白与I型胶原蛋白的相对比例方面未发现显著差异。与四氯化碳组相比,维生素A预处理组肝脏SGAG总量的绝对增加伴随着硫酸皮肤素浓度更显著的增加(硫酸皮肤素与硫酸乙酰肝素的比例:四氯化碳组为1.15,维生素A预处理组为1.70)。与仅接受四氯化碳处理的大鼠肝脏中发现的硫酸皮肤素相比,最后一组中的硫酸皮肤素很大一部分分子量更高。我们的结果表明,维生素A预处理可改变肝脏胶原蛋白和SGAG沉积,并可抑制或延缓长期用四氯化碳处理大鼠肝硬化的发展。我们推测这种作用可能是由于维生素A诱导的贮脂(伊托)细胞表型的改变。