Safaeian L, Jafarian A, Rabbani M, Sadeghi H M, Torabinia N, Alavi S A
Department of Pharmacology and Toxicology, Faculty of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Hezar Jarib Avenue, Isfahan, Iran.
Pak J Biol Sci. 2008 Dec 1;11(23):2606-12. doi: 10.3923/pjbs.2008.2606.2612.
This study hypothesized that the expression of apoptosis-regulatory genes, such as BCL-2 and BAX may be affected by genetic variation in bleomycin-induced pulmonary fibrosis in C57BL/6 and NMRI mice. Pulmonary fibrosis induced by single intratracheal dose of bleomycin (3 U kg(-1)). After 2 weeks, lung samples were analyzed for collagen deposition, pathological changes and expression of BCL-2 and BAX. The fibrotic lung changes were similar in both strains. The immunohistochemical assay using a biotin-streptavidin technique showed no significant difference in immunoreactivity for BCL-2 protein between the controls and bleomycin-treated C57BL/6 mice. However, in NMRI mice, the expression of BCL-2 was significantly (p<0.05) upregulated in myofibroblasts and neutrophils. The expression of BAX protein was significantly (p<0.05) upregulated in alveolar epithelial cells of both strains and downregulated in myofibroblasts and lymphocytes of the lung tissues of C57BL/6 mice and also in lymphocytes of NMRI mice at 2 weeks after bleomycin instillation. These results confirm the role of BCL-2 and BAX proteins in the pathogenesis of pulmonary fibrosis and suggest that the expression of apoptotic regulatory genes may be specific in different cell types in various strains.
本研究假设，诸如BCL-2和BAX等凋亡调节基因的表达可能受博来霉素诱导的C57BL/6和NMRI小鼠肺纤维化中基因变异的影响。通过气管内单次注射博来霉素（3 U kg(-1)）诱导肺纤维化。2周后，分析肺样本中的胶原沉积、病理变化以及BCL-2和BAX的表达。两种品系的肺纤维化变化相似。使用生物素-链霉亲和素技术的免疫组织化学分析显示对照小鼠与经博来霉素处理的C57BL/6小鼠之间BCL-2蛋白的免疫反应性无显著差异。然而，在NMRI小鼠中，肌成纤维细胞和中性粒细胞中BCL-2的表达显著上调（p<0.05）。博来霉素滴注2周后，两种品系的肺泡上皮细胞中BAX蛋白的表达均显著上调（p<0.05），而在C57BL/6小鼠肺组织的肌成纤维细胞和淋巴细胞以及NMRI小鼠的淋巴细胞中BAX蛋白的表达下调。这些结果证实了BCL-2和BAX蛋白在肺纤维化发病机制中的作用，并表明凋亡调节基因的表达在不同品系的不同细胞类型中可能具有特异性。
