Cerbón-Ambriz J, Cerbón-Solórzano J, Rojkind M
Department of Biochemistry, Centro de Investigación y de Estudios Avanzados del IPN, Mexico City, Mexico 07000.
Hepatology. 1991 Mar;13(3):551-6.
Previous work has shown that lactic acid, and to a lesser extent pyruvic acid, is able to increase collagen synthesis significantly in liver slices of CCl4-treated rats but not normal rats. The purpose of this report is to document which cells in the cirrhotic liver are responsible for the lactate-stimulated increase in collagen synthesis. It was found that (a) incorporation of 3H-proline into protein-bound 3H-hydroxyproline is increased threefold to fourfold in hepatocytes from CCl4-treated rats as compared with normal rat hepatocytes; (b) neither the hepatocytes from normal nor those from CCl4-treated rats modify their collagen synthesizing capacity when 30 mmol/L lactic acid was added to the incubation medium; (c) nonparenchymal cells obtained from livers of CCl4-treated rats synthesize much less collagen than hepatocytes, but their synthesis is stimulated twofold by lactic acid; (d) from the different nonparenchymal cells, only fat-storing (Ito) cells increase collagen synthesis when lactic acid is present in the incubation medium. These results suggest that the increased lactic acid levels observed in patients with alcoholic hepatic cirrhosis may play an important role in the development of fibrosis by stimulating collagen production by fat-storing (Ito) cells.
先前的研究表明，乳酸以及程度较轻的丙酮酸，能够显著增加四氯化碳处理的大鼠肝脏切片中的胶原蛋白合成，但对正常大鼠则无此作用。本报告的目的是确定肝硬化肝脏中哪些细胞负责乳酸刺激的胶原蛋白合成增加。研究发现：（a）与正常大鼠肝细胞相比，四氯化碳处理的大鼠肝细胞中3H-脯氨酸掺入蛋白质结合的3H-羟脯氨酸增加了三到四倍；（b）当向孵育培养基中添加30 mmol/L乳酸时，正常大鼠和四氯化碳处理的大鼠的肝细胞均未改变其胶原蛋白合成能力；（c）从四氯化碳处理的大鼠肝脏中获得的非实质细胞合成的胶原蛋白比肝细胞少得多，但乳酸可使其合成增加两倍；（d）在不同的非实质细胞中，只有贮脂（伊托）细胞在孵育培养基中存在乳酸时会增加胶原蛋白合成。这些结果表明，酒精性肝硬化患者中观察到的乳酸水平升高可能通过刺激贮脂（伊托）细胞产生胶原蛋白，在纤维化发展中起重要作用。
