Lopes-Pacheco Miquéias, Xisto Debora G, Ornellas Felipe M, Antunes Mariana A, Abreu Soraia C, Rocco Patricia R M, Takiya Christina M, Morales Marcelo M
Laboratory of Cellular and Molecular Physiology, Carlos Chagas Filho Biophysics Institute, Federal University of Rio de Janeiro, Brazil.
Cell Physiol Biochem. 2013;32(6):1681-94. doi: 10.1159/000356603. Epub 2013 Dec 13.
BACKGROUND/AIMS: Bone marrow-derived cells (BMDCs) reduced mechanical and histologic changes in the lung in a murine model of silicosis, but these beneficial effects did not persist in the course of lung injury. We hypothesized that repeated administration of BMDCs may decrease lung inflammation and remodeling thus preventing disease progression.
One hundred and two C57BL/6 mice were randomly divided into SIL (silica, 20 mg intratracheally [IT]) and control (C) groups (saline, IT). C and SIL groups were further randomized to receive BMDCs (2×10(6) cells) or saline IT 15 and 30 days after the start of the protocol.
By day 60, BMDCs had decreased the fractional area of granuloma and the number of polymorphonuclear cells, macrophages (total and M1 phenotype), apoptotic cells, the level of transforming growth factor (TGF)-β' and types I and III collagen fiber content in the granuloma. In the alveolar septa, BMDCs reduced the amount of collagen and elastic fibers, TGF-β, and the number of M1 and apoptotic cells. Furthermore, interleukin (IL)-1β, IL-1R1, caspase-3 mRNA levels decreased and the level of IL-1RN mRNA increased. Lung mechanics improved after BMDC therapy. The presence of male donor cells in lung tissue was not observed using detection of Y chromosome DNA.
repeated administration of BMDCs reduced inflammation, fibrogenesis, and elastogenesis, thus improving lung mechanics through the release of paracrine factors.
背景/目的：在矽肺小鼠模型中，骨髓来源的细胞（BMDCs）可减轻肺部的机械性和组织学变化，但这些有益作用在肺损伤过程中并未持续存在。我们推测，重复给予BMDCs可能会减轻肺部炎症和重塑，从而预防疾病进展。
102只C57BL/6小鼠被随机分为矽肺组（二氧化硅，经气管内[IT]注入20mg）和对照组（C组，生理盐水，IT注入）。C组和矽肺组在实验开始后15天和30天进一步随机分为接受BMDCs（2×10⁶个细胞）或生理盐水IT注入组。
到第60天时，BMDCs减少了肉芽肿的面积分数、多形核细胞、巨噬细胞（总数和M1表型）、凋亡细胞的数量，降低了转化生长因子（TGF）-β'水平以及肉芽肿中I型和III型胶原纤维含量。在肺泡间隔中，BMDCs减少了胶原和弹性纤维的数量、TGF-β以及M1和凋亡细胞的数量。此外，白细胞介素（IL）-1β、IL-1R1、半胱天冬酶-3 mRNA水平降低，而IL-1RN mRNA水平升高。BMDC治疗后肺力学得到改善。通过检测Y染色体DNA未观察到肺组织中有雄性供体细胞。
重复给予BMDCs可减轻炎症、纤维生成和弹性生成，从而通过旁分泌因子的释放改善肺力学。
