Department of Emergency and Critical Care Medicine, Wakayama Medical University, 811-1 Kimiidera, Wakayama 641-8509, Japan.
Department of Anatomy and Cell Biology, Wakayama Medical University, 811-1 Kimiidera, Wakayama 641-8509, Japan.
Int J Mol Sci. 2023 Nov 9;24(22):16108. doi: 10.3390/ijms242216108.
In our preliminary experiment, peritoneal sclerosis likely induced by peritoneal dialysis was unexpectedly observed in the livers of rats given bleomycin and lansoprazole. We examined whether this peritoneal thickening around the liver was time-dependently induced by administration of both drugs. Male Wistar rats were injected with bleomycin and/or lansoprazole for 2 or 4 weeks. The 3YB-1 cell line derived from rat fibroblasts was treated by bleomycin and/or lansoprazole for 24 h. The administration of both drugs together, but not individually, thickened the peritoneal tissue around the liver. There was accumulation of collagen fibers, macrophages, and eosinophils under mesothelial cells. Expressions of , and genes were increased in the peritoneal tissue around the liver and in 3YB-1 cells by the administration of both drugs together, and genes had increased expressions in this tissue and 3YB-1 cells. Mesothelial cells indicated immunoreactivity against both cytokeratin, a mesothelial cell marker, and αSMA, a fibroblast marker, around the livers of rats given both drugs. Administration of both drugs induced the migration of macrophages and eosinophils and induced fibrosis associated with the possible activation of fibroblasts and the possible promotion of the mesothelial-mesenchymal transition. This might become a novel model of peritoneal sclerosis for peritoneal dialysis.
在我们的初步实验中,出乎意料地观察到给予博来霉素和兰索拉唑的大鼠肝脏中出现腹膜透析引起的腹膜硬化。我们研究了这两种药物给药是否会导致肝脏周围腹膜的增厚具有时间依赖性。雄性 Wistar 大鼠接受博来霉素和/或兰索拉唑注射 2 或 4 周。将博来霉素和/或兰索拉唑处理源自大鼠成纤维细胞的 3YB-1 细胞系 24 小时。两种药物联合给药而不是单独给药会使肝周围腹膜组织增厚。在间皮细胞下积累了胶原纤维、巨噬细胞和嗜酸性粒细胞。两种药物联合给药可使肝周围腹膜组织和 3YB-1 细胞中 、 和 基因的表达增加,而这两种组织和 3YB-1 细胞中的 基因表达增加。在给予两种药物的大鼠的肝脏周围,间皮细胞对细胞角蛋白(一种间皮细胞标志物)和αSMA(一种成纤维细胞标志物)均表现出免疫反应性。两种药物的联合给药诱导巨噬细胞和嗜酸性粒细胞的迁移,并诱导与成纤维细胞的可能激活和间皮-间质转化的可能促进相关的纤维化。这可能成为腹膜透析的腹膜硬化的新型模型。