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弹性蛋白酶诱导肺气肿动物模型中气管内滴注脂多糖引起的急性肺损伤。

Acute Lung Injury in Response to Intratracheal Instillation of Lipopolysaccharide in an Animal Model of Emphysema Induced by Elastase.

机构信息

Pulmonary Research Laboratory, Federal University of Juiz de Fora, Av. Eugênio do Nascimento - s/n°, Dom Bosco, Juiz de Fora, Minas Gerais, 36038-330, Brazil.

Department of Morphology, Institute of Biological Sciences, Federal University of Juiz de Fora, Rua José Lourenço Khelmer - s/n, Campus Universitário, São Pedro, Juiz de Fora, Minas Gerais, 36036-900, Brazil.

出版信息

Inflammation. 2018 Feb;41(1):174-182. doi: 10.1007/s10753-017-0675-5.

Abstract

The response of lungs with emphysema to an acute lung injury (ALI) remains unclear. This study compared the lung response to intratracheal instillation of lipopolysaccharide (LPS) in rats with and without emphysema. Twenty-four Wistar rats were randomized to four groups: control group (C-G), ALI group (ALI-G), emphysema group (E-G), emphysema and ALI group (E-ALI-G). Euthanasia and the following analysis were performed 24 h after ALI induction: lung histology, bronchoalveolar lavage (BAL), mRNA expression of inflammatory mediators, and blood gas measures. The histological analysis showed that animals of ALI-G (0.55 ± 0.15) and E-ALI-G (0.69 ± 0.08) had a higher ALI score compared to C-G (0.12 ± 0.04) and E-G (0.16 ± 0.04) (p < 0.05). The analysis of each component of the score demonstrated that ALI-G and E-ALI-G had greater alveolar and interstitial neutrophil infiltration, as well as greater amount of alveolar proteinaceous debris. Comparing the two groups that received LPS, there was a trend of higher ALI in the E-ALI-G, specially due to a higher neutrophil infiltration in the alveolar spaces and a higher septal thickening. Total cell count (E-G = 3.09 ± 0.83; ALI-G = 4.45 ± 1.9; E-ALI-G = 5.9 ± 2.1; C-G = 0.73 ± 0.37 × 10) and neutrophil count (E-G = 0.69 ± 0.35; ALI-G = 2.53 ± 1.09; E-ALI-G = 3.86 ± 1.4; C-G = 0.09 ± 0.07 × 10) in the BAL were higher in the groups E-G, ALI-G, and E-ALI-G when compared to C-G (p < 0.05). The IL-6, TNF-α, and CXCL2 mRNA expressions were higher in the animals that received LPS (ALI-G and E-ALI-G) compared to the C-G and E-G (p < 0.05). No statistically significant difference was observed in the BAL cellularity and in the expression of inflammatory mediators between the ALI-G and the E-ALI-G. The severity of ALI in response to intratracheal instillation of LPS did not show difference in rats with and without intratracheal-induced emphysema.

摘要

肺气肿肺对急性肺损伤(ALI)的反应尚不清楚。本研究比较了气管内滴注脂多糖(LPS)后伴有和不伴有肺气肿的大鼠的肺反应。将 24 只 Wistar 大鼠随机分为四组:对照组(C-G)、ALI 组(ALI-G)、肺气肿组(E-G)、肺气肿和 ALI 组(E-ALI-G)。在诱导 ALI 后 24 小时进行安乐死和以下分析:肺组织学、支气管肺泡灌洗(BAL)、炎症介质的 mRNA 表达和血气测量。组织学分析显示,与 C-G(0.12±0.04)和 E-G(0.16±0.04)相比,ALI-G(0.55±0.15)和 E-ALI-G(0.69±0.08)的 ALI 评分更高(p<0.05)。对评分的每个组成部分进行分析表明,ALI-G 和 E-ALI-G 具有更大的肺泡和间质中性粒细胞浸润以及更大的肺泡蛋白性碎片。比较两组接受 LPS 的大鼠,E-ALI-G 的 ALI 趋势更高,特别是由于肺泡空间的中性粒细胞浸润更高和隔增厚更高。总细胞计数(E-G=3.09±0.83;ALI-G=4.45±1.9;E-ALI-G=5.9±2.1;C-G=0.73±0.37×10)和 BAL 中的中性粒细胞计数(E-G=0.69±0.35;ALI-G=2.53±1.09;E-ALI-G=3.86±1.4;C-G=0.09±0.07×10)在 E-G、ALI-G 和 E-ALI-G 组中均高于 C-G 组(p<0.05)。与 C-G 和 E-G 相比,接受 LPS 的动物(ALI-G 和 E-ALI-G)的 IL-6、TNF-α 和 CXCL2 mRNA 表达更高(p<0.05)。在 ALI-G 和 E-ALI-G 之间,BAL 细胞数和炎症介质的表达没有统计学差异。在气管内滴注 LPS 后,有无气管内诱导肺气肿的大鼠的 ALI 严重程度没有差异。

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