Early Peritoneal Dialysis Ameliorates Blast Lung Injury by Alleviating Pulmonary Edema and Inflammation.
- 作者列表："Chen K","Yang J","Xiao F","Chen J","Hu W","Wang X","Wang L","Du J","Jiang J","He Y
BACKGROUND:Blast lung injury is a high-energy trauma with high mortality for explosion victims. A treatment for blast lung injury is still lacking. The aim of this study was to observe the efficacy and mechanism of peritoneal dialysis combined with glucocorticoids (GC) in the treatment of blast lung injury in rats. METHODS:Rats were randomly divided into five groups: control, sham, GC, peritoneal dialysis (dialysis for short), and dialysis + GC groups. All rats were injured by a biological shock tube-I. RESULTS:The lung water levels in the dialysis group and dialysis + GC group were significantly lower than that in the control group at 6 and 24 h after blast injury. The oxygenation index, forced vital capacity, maximum midexpiratory flow, and functional residual capacity of rats in the dialysis and dialysis + GC groups were significantly higher than those in the control group. The serum levels of interleukin (IL)-1β, IL-6, tumor necrosis factor- α, monocyte chemoattractant protein-1, C-reactive protein, and IL-10 in the dialysis and dialysis + GC groups were significantly lower than those in the control group. Genome-wide mRNA microarray results showed that the aquaporin 1 level in the lung tissue of the dialysis group was 6.67 times higher than that in the control group. CONCLUSION:Early peritoneal dialysis can attenuate pulmonary edema and inflammation, and protect acute lung injury after blast injury.
背景: 爆炸肺损伤是一种高能量创伤，死亡率较高。爆炸肺损伤的治疗仍然缺乏。本研究观察腹膜透析联合糖皮质激素 (GC) 治疗大鼠肺损伤的疗效及机制。 方法: 大鼠随机分为 5 组: 对照组、假手术组、 GC 组、腹膜透析 (简称透析) 组、透析 + GC 组。所有大鼠均被生物休克管-I 损伤。 结果: 冲击伤后 6 、 24 h，透析组和透析 + GC 组肺含水量明显低于对照组。透析组和透析 + GC 组大鼠氧合指数、用力肺活量、最大肺血流量、功能残气量均显著高于对照组。血清白细胞介素 (IL)-1 β 、 IL-6 、肿瘤坏死因子-α 、单核细胞趋化蛋白-1 、 C 反应蛋白、透析组和透析 + GC 组 IL-10 明显低于对照组。全基因组 mRNA 芯片结果显示，透析组肺组织水通道蛋白 1 水平是对照组的 6.67 倍。 结论: 早期腹膜透析可减轻冲击伤后肺水肿和炎症反应，保护急性肺损伤。
METHODS:BACKGROUND AND PURPOSE:A critical role for sphingosine kinase/sphingosine-1-phosphate (S1P) pathway in the control of airway function has been demonstrated in respiratory diseases. Here, we address S1P contribution in a mouse model of mild chronic obstructive pulmonary disease (COPD). EXPERIMENTAL APPROACH:C57BL/6J mice have been exposed to room air or cigarette smoke up to 11 months and killed at different time points. Functional and molecular studies have been performed. KEY RESULTS:Cigarette smoke caused emphysematous changes throughout the lung parenchyma coupled to a progressive collagen deposition in both peribronchiolar and peribronchial areas. The high and low airways showed an increased reactivity to cholinergic stimulation and α-smooth muscle actin overexpression. Similarly, an increase in airway reactivity and lung resistances following S1P challenge occurred in smoking mice. A high expression of S1P, Sph-K2 , and S1P receptors (S1P2 and S1P3 ) has been detected in the lung of smoking mice. Sphingosine kinases inhibition reversed the increased cholinergic response in airways of smoking mice. CONCLUSIONS AND IMPLICATIONS:S1P signalling up-regulation follows the disease progression in smoking mice and is involved in the development of airway hyperresponsiveness. Our study defines a therapeutic potential for S1P inhibitors in management of airways hyperresponsiveness associated to emphysema in smokers with both asthma and COPD.
METHODS::The interim results from this 90-day multi-dose, inhalation toxicology study with life-time post-exposure observation has shown an important fundamental difference in persistence and pathological response in the lung between brake dust derived from brake-pads manufactured with chrysotile, TiO2 or chrysotile alone in comparison to the amphiboles, crocidolite and amosite asbestos. In the brake dust exposure groups no significant pathological response was observed at any time. Slight macrophage accumulation of particles was noted. Wagner-scores, were from 1 to 2 (1 = air-control group) and were similar to the TiO2 group. Chrysotile being biodegradable, shows a weakening of its matrix and breaking into short fibers & particles that can be cleared by alveolar macrophages and continued dissolution. In the chrysotile exposure groups, particle laden macrophage accumulation was noted leading to a slight interstitial inflammatory response (Wagner-score 1-3). There was no peribronchiolar inflammation and occasional very slight interstitial fibrosis. The histopathology and the confocal analyses clearly differentiate the pathological response from amphibole asbestos, crocidolite and amosite, compared to that from the brake dust and chrysotile. Both crocidolite and amosite induced persistent inflammation, microgranulomas, and fibrosis (Wagner-scores 4), which persisted through the post exposure period. The confocal microscopy of the lung and snap-frozen chestwalls quantified the extensive inflammatory response and collagen development in the lung and on the visceral and parietal surfaces. The interim results reported here, provide a clear basis for differentiating the effects from brake dust exposure from those following amphibole asbestos exposure. The subsequent results through life-time post-exposure will follow.
METHODS::The respiratory tract is lined by a pseudo-stratified epithelium from the nose to terminal bronchioles. This first line of defense of the lung against external stress includes five main cell types: basal, suprabasal, club, goblet and multiciliated cells, as well as rare cells such as ionocytes, neuroendocrine and tuft/brush cells. At homeostasis, this epithelium self-renews at low rate but is able of fast regeneration upon damage. Airway epithelial cell lineages during regeneration have been investigated in the mouse by genetic labeling, mainly after injuring the epithelium with noxious agents. From these approaches, basal cells have been identified as progenitors of club, goblet and multiciliated cells, but also of ionocytes and neuroendocrine cells. Single-cell RNA sequencing, coupled to lineage inference algorithms, has independently allowed the establishment of comprehensive pictures of cell lineage relationships in both mouse and human. In line with genetic tracing experiments in mouse trachea, studies using single-cell RNA sequencing (RNAseq) have shown that basal cells first differentiate into club cells, which in turn mature into goblet cells or differentiate into multiciliated cells. In the human airway epithelium, single-cell RNAseq has identified novel intermediate populations such as deuterosomal cells, 'hybrid' mucous-multiciliated cells and progenitors of rare cells. Novel differentiation dynamics, such as a transition from goblet to multiciliated cells have also been discovered. The future of cell lineage relationships in the respiratory tract now resides in the combination of genetic labeling approaches with single-cell RNAseq to establish, in a definitive manner, the hallmarks of cellular lineages in normal and pathological situations.