Wang Q, Hyde D M, Giri S N
Department of Veterinary Pharmacology, School of Veterinary Medicine, University of California, Davis.
Lab Invest. 1992 Aug;67(2):234-42.
The bleomycin (BL) hamster model of interstitial pulmonary fibrosis has been widely used to study the pathogenesis of interstitial pulmonary fibrosis and to screen potentially desirable antifibrotic agents. We have recently shown that taurine and niacin in combination, diminished BL-induced increases in lung lipid peroxidation and hydroxyproline content in hamsters. In the present study, we have evaluated the effects of taurine and niacin on the bronchoalveolar lavage (BAL) cells, and morphologic and morphometric features of the lung in the same model of pulmonary fibrosis.
The hamsters were divided into 4 groups: saline; taurine + niacin + saline; BL; and taurine + niacin + BL. Treatment of taurine and niacin began 2 days before the first intratracheal instillation of saline or BL and thereafter daily throughout the study for taurine + niacin + saline and taurine + niacin + BL groups. Hamsters received BL or saline in three consecutive doses at weekly intervals by intratracheal route. Twenty days after the last intratracheal instillation, the hamsters were sacrificed for various studies.
Combined treatment with taurine and niacin suppressed BL-induced inflammation and almost completely abrogated pulmonary fibrosis in hamsters. Two independent studies showed that taurine and niacin in combination significantly reduced BL-induced increases in bronchoalveolar inflammatory cell counts, protein content, and acid phosphatase activity. By both light and electron microscopy, the lungs of hamsters treated with BL and taurine and niacin had much fewer inflammatory cells, less epithelial necrosis and collagen deposition than hamsters treated with BL alone.
The results of this investigation suggest that combined treatment with taurine and niacin is effective against the development of lung fibrosis in the BL-hamster model and offers a novel therapeutic modality in the prevention of the fibrotic processes.
博来霉素(BL)诱导的仓鼠肺间质纤维化模型已被广泛用于研究肺间质纤维化的发病机制,并筛选潜在的理想抗纤维化药物。我们最近发现,牛磺酸和烟酸联合使用可减少博来霉素诱导的仓鼠肺脂质过氧化和羟脯氨酸含量增加。在本研究中,我们评估了牛磺酸和烟酸对同一肺纤维化模型中支气管肺泡灌洗(BAL)细胞以及肺的形态学和形态计量学特征的影响。
将仓鼠分为4组:生理盐水组;牛磺酸+烟酸+生理盐水组;博来霉素组;牛磺酸+烟酸+博来霉素组。牛磺酸和烟酸的治疗在首次气管内注入生理盐水或博来霉素前两天开始,此后牛磺酸+烟酸+生理盐水组和牛磺酸+烟酸+博来霉素组在整个研究过程中每天给药。仓鼠通过气管内途径每周连续三次接受博来霉素或生理盐水注射。在最后一次气管内注入后20天,处死仓鼠进行各项研究。
牛磺酸和烟酸联合治疗可抑制博来霉素诱导的炎症反应,并几乎完全消除仓鼠的肺纤维化。两项独立研究表明,牛磺酸和烟酸联合使用可显著降低博来霉素诱导的支气管肺泡炎症细胞计数、蛋白质含量和酸性磷酸酶活性增加。通过光镜和电镜观察,与单独接受博来霉素治疗的仓鼠相比,接受博来霉素及牛磺酸和烟酸治疗的仓鼠肺内炎症细胞明显减少,上皮坏死和胶原沉积也较少。
本研究结果表明,牛磺酸和烟酸联合治疗对BL-仓鼠模型中的肺纤维化发展有效,并为预防纤维化过程提供了一种新的治疗方式。