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腹腔注射尼古丁处理的大鼠的肺形态测定及基质金属蛋白酶-12表达

Lung morphometry and MMP-12 expression in rats treated with intraperitoneal nicotine.

作者信息

Valença Samuel Santos, de Souza da Fonseca Adenilson, da Hora Katia, Santos Ricardo, Porto Luis Cristóvão

机构信息

Department of Histology and Embryology, Institute of Biology Roberto Alcantara Gomes, State University of Rio de Janeiro, Rio de Janeiro, Brazil.

出版信息

Exp Toxicol Pathol. 2004 Mar;55(5):393-400. doi: 10.1078/0940-2993-00322.

DOI:10.1078/0940-2993-00322
PMID:15088641
Abstract

Nicotine, a toxic tobacco component, plays an important role in the development of cardiovascular and lung diseases in smokers. Our objective was to investigate the effects of the intraperitoneal (i.p.) nicotine treatment in lung morphology. Wistar male rats (3-4 months old) were divided in five groups, a control one, and other groups treated with nicotine (1 mg/kg/day) for 8 days and sacrificed after 24, 48, 96, and 192 h. Morphometry was used to estimate the lung alveolar parenchyme and septal elastic fibers changes, and immunohistochemistry was performed to detect macrophage metalloelastase (MMP-12) and quantify vessels by immunolabelling with alpha-smooth muscle cells. Thickening of the alveolar septa was present in all nicotine groups, and associated with mononuclear cell infiltration, angiogenesis, and irregular areas of collapse. After 96 h, rat lungs showed macrophage, expressing MMP-12, that was also present after 192 h of recovery. Pleural and parenchyma inflammation, fibrosis and macrophage were also seen after 192 h. Intraperitoneal nicotine treated rats exhibited an increase of the volume fraction of alveolar parenchyme, a reduction of volume and surface fraction septal elastic fibers, and an increase of the numerical fraction of microvasculature vessels compared to control ones. MMP-12 was detected in groups of macrophages Wistar rats lung exhibited a progressive morphological damage after 192 hours of recovery, after 8 daily doses of 1 mg/kg body weight on i.p. nicotine.

摘要

尼古丁是一种有毒的烟草成分,在吸烟者心血管疾病和肺部疾病的发展中起重要作用。我们的目的是研究腹腔注射尼古丁对肺部形态的影响。将3至4个月大的雄性Wistar大鼠分为五组,一组为对照组,其他组用尼古丁(1毫克/千克/天)治疗8天,并在24、48、96和192小时后处死。采用形态计量学方法评估肺肺泡实质和间隔弹性纤维的变化,并进行免疫组织化学检测巨噬细胞金属弹性蛋白酶(MMP-12),并用α平滑肌细胞免疫标记定量血管。所有尼古丁组均出现肺泡间隔增厚,并伴有单核细胞浸润、血管生成和不规则塌陷区域。96小时后,大鼠肺中出现表达MMP-12的巨噬细胞,在恢复192小时后也存在。192小时后还可见胸膜和实质炎症、纤维化和巨噬细胞。与对照组相比,腹腔注射尼古丁治疗的大鼠肺泡实质体积分数增加,间隔弹性纤维体积和表面分数减少,微血管数量分数增加。在Wistar大鼠肺巨噬细胞组中检测到MMP-12,在腹腔注射尼古丁每天1毫克/千克体重共8天、恢复192小时后,肺呈现进行性形态学损伤。

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