Blaisdell R J, Schiedt M J, Giri S N
Department of Veterinary Pharmacology and Toxicology, University of California, Davis 95616.
J Biochem Toxicol. 1994 Apr;9(2):79-86. doi: 10.1002/jbt.2570090205.
Taurine and niacin have been previously found to block the accumulation of collagen in lung in the multidose bleomycin hamster model of pulmonary fibrosis. Previous studies have found an increase in the pulmonary collagen cross-links dihydroxylysinonoroleucine (DHLNL) and hydroxypyridinium (OHP) in the single dose bleomycin rat model. In this study, we asked if taurine and niacin would block the increase in DHLNL and OHP in the multidose bleomycin hamster model of lung fibrosis. Hamsters were intratracheally instilled with three consecutive doses of saline or bleomycin sulfate 1 week apart (2.5, 2.0, 1.5 units/5 mL/kg). Animals were fed diet containing either 2.5% niacin and 2.5% taurine or control diet throughout the experiment. The four groups were saline-instilled with control diet (SCD), bleomycin instilled with control diet (BCD), bleomycin-instilled with taurine-niacin in diet (BTN), and saline-instilled with taurine-niacin in diet (STN). Animals were sacrificed at 1, 4, and 8 weeks after the last bleomycin instillation. Hydroxyproline per lung in the BCD group was significantly elevated by 38, 56, and 60% over the SCD group at 1, 4, and 8 weeks, respectively. There were no statistically significant differences among the four groups in DHLNL (mmole) per mole collagen at the 1 or 8 week time point. At four weeks, DHLNL was significantly elevated by 46.4% in the BCD group over the SCD group. The OHP (mmole) per mole of collagen at 1 and 4 weeks in the BCD group was not statistically different from the SCD group.(ABSTRACT TRUNCATED AT 250 WORDS)
先前已发现,在多剂量博来霉素诱导的肺纤维化仓鼠模型中,牛磺酸和烟酸可阻止肺中胶原蛋白的积累。先前的研究发现,在单剂量博来霉素诱导的大鼠模型中,肺胶原蛋白交联物二羟基赖氨酸正亮氨酸(DHLNL)和羟基吡啶鎓(OHP)有所增加。在本研究中,我们探究了牛磺酸和烟酸是否会阻止多剂量博来霉素诱导的肺纤维化仓鼠模型中DHLNL和OHP的增加。仓鼠每隔1周经气管内连续滴注三次生理盐水或硫酸博来霉素(2.5、2.0、1.5单位/5 mL/千克)。在整个实验过程中,给动物喂食含2.5%烟酸和2.5%牛磺酸的饲料或对照饲料。四组分别为滴注生理盐水并喂食对照饲料(SCD)、滴注博来霉素并喂食对照饲料(BCD)、滴注博来霉素并在饲料中添加牛磺酸-烟酸(BTN)、滴注生理盐水并在饲料中添加牛磺酸-烟酸(STN)。在最后一次滴注博来霉素后的1、4和8周处死动物。在第1、4和8周时,BCD组每只肺的羟脯氨酸分别比SCD组显著升高38%、56%和60%。在第1周或第8周时间点,四组每摩尔胶原蛋白中DHLNL(毫摩尔)含量无统计学显著差异。在第4周时,BCD组的DHLNL比SCD组显著升高46.4%。BCD组在第1周和第4周时每摩尔胶原蛋白的OHP(毫摩尔)与SCD组无统计学差异。(摘要截断于250字)