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骨髓源性单核细胞对慢性变应性炎症小鼠模型气道和肺实质重塑的影响。

Effects of bone marrow-derived mononuclear cells on airway and lung parenchyma remodeling in a murine model of chronic allergic inflammation.

机构信息

Laboratory of Pulmonary Investigation, Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil.

出版信息

Respir Physiol Neurobiol. 2011 Jan 31;175(1):153-63. doi: 10.1016/j.resp.2010.10.006. Epub 2010 Nov 2.

Abstract

We hypothesized that bone marrow-derived mononuclear cells (BMDMC) would attenuate the remodeling process in a chronic allergic inflammation model. C57BL/6 mice were assigned to two groups. In OVA, mice were sensitized and repeatedly challenged with ovalbumin. Control mice (C) received saline under the same protocol. C and OVA were further randomized to receive BMDMC (2 × 10⁶) or saline intravenously 24 h before the first challenge. BMDMC therapy reduced eosinophil infiltration, smooth muscle-specific actin expression, subepithelial fibrosis, and myocyte hypertrophy and hyperplasia, thus causing a decrease in airway hyperresponsiveness and lung mechanical parameters. BMDMC from green fluorescent protein (GFP)-transgenic mice transplanted into GFP-negative mice yielded lower engraftment in OVA. BMDMC increased insulin-like growth factor expression, but reduced interleukin-5, transforming growth factor-β, platelet-derived growth factor, and vascular endothelial growth factor mRNA expression. In conclusion, in the present chronic allergic inflammation model, BMDMC therapy was an effective pre-treatment protocol that potentiated airway epithelial cell repair and prevented inflammatory and remodeling processes.

摘要

我们假设骨髓来源的单核细胞(BMDMC)将减轻慢性过敏炎症模型中的重塑过程。C57BL/6 小鼠被分为两组。在 OVA 组中,小鼠用卵清蛋白致敏并反复挑战。对照小鼠(C)在相同方案下接受生理盐水。C 和 OVA 进一步随机接受 BMDMC(2×10⁶)或生理盐水静脉注射,在第一次挑战前 24 小时。BMDMC 治疗减少了嗜酸性粒细胞浸润、平滑肌特异性肌动蛋白表达、黏膜下纤维化以及肌细胞肥大和增生,从而导致气道高反应性和肺力学参数降低。从绿色荧光蛋白(GFP)转基因小鼠移植到 GFP 阴性小鼠的 BMDMC 植入率较低。BMDMC 增加了胰岛素样生长因子的表达,但减少了白细胞介素 5、转化生长因子-β、血小板衍生生长因子和血管内皮生长因子 mRNA 的表达。总之,在本慢性过敏炎症模型中,BMDMC 治疗是一种有效的预处理方案,增强了气道上皮细胞修复并预防了炎症和重塑过程。

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