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气管内注入木瓜蛋白酶诱导大鼠实验性肺气肿的形态发生:弹性纤维的变化

Morphogenesis of rat experimental pulmonary emphysema induced by intratracheally administered papain: changes in elastic fibres.

作者信息

Pastor L M, Sánchez-Gascón F, Girona J C, Bernal-Mañas C M, Morales E, Beltrán-Frutos E, Canteras M

机构信息

Department of Cell Biology, Medical School, Aging Institute, University of Murcia, Murcia, Spain.

出版信息

Histol Histopathol. 2006 Dec;21(12):1309-19. doi: 10.14670/HH-21.1309.

Abstract

The ultrastructural changes of elastic fibres in emphysematous lungs have been studied in men, but few works exist on this topic in experimental emphysematous animals. In this paper, the morphogenesis of emphysema and alterations of the elastic fibres produced by the instillation of papain are described by light and electron microscopy. Wistar rats were instilled through the trachea with papain at a rate of 3 mg/100 g animal weight. The animals were sacrificed 12 h, 3 days, 10 days and 60 days after enzyme instillation. The "Mean Linear Intercept" (MLI), the "Number of fenestrations/respiratory units" (NF) the "Number of macrophages per mm of alveolar wall" (NM) and the "Number of respiratory unit/mm2" (RU), both in the control and experimental groups were studied. Two months after treatment, the experimental group showed a strong increase in the MLI (p<0.001) and NF (p<0.001), and a diminished number of RU (p<0.05) compared with the control group. Partial correlation analysis showed a positive correlation only between MLI and NF. Twelve hours after papain instillation an inflammatory response was observed, the elastic fibres were ruptured, while the microfibrilar component remained. New formations of eulanin elastic fibres were observed three days post papain instillation. After ten days the interalveolar oedema had disappeared and the elastic fibres were of normal morphology although irregular groups of strips of elastic fibres were evident. A mixed pattern of panlobular, centrilobular and normal lung zones were observed. Two months after papain instillation abundant accumulations of elastic fibres of irregular outline were observed associated to collagen fibres. In conclusion, the morphometric parameters studied showed a significant progression of the emphysema. The strong correlation between NF and MLI suggested that papain-induced emphysema is principally caused by breaches of the alveolar walls. The results seem to point to a very abnormal remodelling process associated with elastic fibre regeneration, although there were no signs of destruction of these new fibres formed in emphysematous rat lung induced by papain.

摘要

人们已经对人类肺气肿肺组织中弹性纤维的超微结构变化进行了研究,但关于实验性肺气肿动物的这一主题的研究却很少。在本文中,通过光学显微镜和电子显微镜描述了木瓜蛋白酶滴注诱导的肺气肿的形态发生以及弹性纤维的变化。将木瓜蛋白酶以3mg/100g动物体重的剂量经气管滴注到Wistar大鼠体内。在酶滴注后12小时、3天、10天和60天处死动物。研究了对照组和实验组的“平均线性截距”(MLI)、“每呼吸单位的窗孔数量”(NF)、“每毫米肺泡壁的巨噬细胞数量”(NM)以及“每平方毫米的呼吸单位数量”(RU)。治疗两个月后,与对照组相比,实验组的MLI(p<0.001)和NF(p<0.001)显著增加,而RU数量减少(p<0.05)。偏相关分析显示仅MLI和NF之间存在正相关。木瓜蛋白酶滴注12小时后观察到炎症反应,弹性纤维断裂,而微纤维成分保留。木瓜蛋白酶滴注3天后观察到优球蛋白弹性纤维的新形成。10天后肺泡间水肿消失,弹性纤维形态正常,尽管可见不规则的弹性纤维条带组。观察到全小叶、小叶中心和正常肺区的混合模式。木瓜蛋白酶滴注两个月后,观察到与胶原纤维相关的轮廓不规则的弹性纤维大量积聚。总之,所研究的形态计量学参数显示肺气肿有显著进展。NF和MLI之间的强相关性表明木瓜蛋白酶诱导的肺气肿主要是由肺泡壁破裂引起的。结果似乎表明存在与弹性纤维再生相关的非常异常的重塑过程,尽管在木瓜蛋白酶诱导的肺气肿大鼠肺中形成的这些新纤维没有破坏迹象。

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