Blaisdell R J, Giri S N
Department of Molecular Biosciences, School of Veterinary Medicine, University of California, Davis 95616, USA.
J Biochem Toxicol. 1995 Aug;10(4):203-10. doi: 10.1002/jbt.2570100404.
In the multiple-dose bleomycin-hamster model of pulmonary fibrosis, combined treatment with taurine and niacin blocks the increase in lung collagen deposition. We investigated the effects of taurine and niacin on lung lysyl oxidase and type I collagenase activities in this model. Hamsters were intratracheally instilled with three weekly doses of saline or bleomycin sulfate. Animals were fed either a diet containing 2.5% niacin and 2.5% taurine, or a control diet throughout the experiment. The four groups were saline-instilled with the control diet (BCD), bleomycin-instilled with the diet containing taurine and niacin (BTN), and saline-instilled with the diet containing taurine and niacin (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. Lysyl oxidase activity per lung in the BCD group was significantly elevated by 57.5 and 91.4% over the SCD controls at 1 and 4 week time periods, respectively. Type I collagenase activity per lung in the BCD group was significantly elevated by 65 and 80% over the SCD controls at 1 and 4 weeks, respectively. The combined treatment with taurine and niacin abolished the bleomycin-induced increases in the lung hydroxyproline content and lysyl oxidase and collagenase activities. It was postulated that one of the mechanisms for the antifibrotic effect of taurine and niacin may be the blockage of bleomycin-induced increases in the lung lysyl oxidase and collagenase activities.
在博来霉素诱导的仓鼠肺纤维化多剂量模型中,牛磺酸和烟酸联合治疗可阻止肺胶原沉积增加。我们在该模型中研究了牛磺酸和烟酸对肺赖氨酰氧化酶及I型胶原酶活性的影响。仓鼠每周经气管内滴注三次生理盐水或硫酸博来霉素。在整个实验过程中,动物分别喂食含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(BCD)、滴注博来霉素并喂食含牛磺酸和烟酸的饲料(BTN)、滴注生理盐水并喂食含牛磺酸和烟酸的饲料(STN)。在最后一次滴注博来霉素后的1、4和8周处死动物。BCD组每只肺的羟脯氨酸含量在1、4和8周时分别比SCD组显著升高38%、56%和60%。BCD组每只肺的赖氨酰氧化酶活性在1周和4周时分别比SCD对照组显著升高57.5%和91.4%。BCD组每只肺的I型胶原酶活性在1周和4周时分别比SCD对照组显著升高65%和80%。牛磺酸和烟酸联合治疗消除了博来霉素诱导的肺羟脯氨酸含量、赖氨酰氧化酶和胶原酶活性的增加。据推测,牛磺酸和烟酸抗纤维化作用的机制之一可能是阻止博来霉素诱导的肺赖氨酰氧化酶和胶原酶活性增加。