Christensen T G, Korthy A L, Snider G L, Hayes J A
J Clin Invest. 1977 Mar;59(3):397-404. doi: 10.1172/JCI108652.
A single intratracheal instillation of pancreatic elastase in hamsters induces a lesion resembling human panacinar emphysema. This paper reports the occurrence of irreversible goblet cell metaplasia in the bronchial epithelium of hamsters similarly exposed to elastase. The goblet cell change was dose related; a dose of 0.1 mg/100 g body wt or less at 16 days, produced slight or moderate goblet cell metaplasia in fewer than half the animals, whereas 84% of animals treated with a dose between 0.2 and 0.5 mg/100 g body wt developed goblet cell metaplastic lesions, more than half of which were considered to be severe. The percentage of goblet cells in the epithelium of elastase-treated hamsters (32.5) was significantly higher (P less than 0.005) than that of unexposed (12.2) and saline-exposed controls (18.7). All hamsters examined 6 and 12 mo after elastase treatment showed the lesion. The pathogenesis of the changes is unclear but the possibility is raised that the bronchial changes may be due to disturbance of an endogenous protease-antiprotease system. The findings suggest the hypothesis that, under appropriate circumstances, a single pulmonary insult in man could lead to a permanent lung injury demonstrating the anatomic lesions of both chronic bronchitis and panacinar emphysema.
对仓鼠进行一次气管内注射胰弹性蛋白酶可诱发一种类似于人类全腺泡型肺气肿的病变。本文报道了同样暴露于弹性蛋白酶的仓鼠支气管上皮中出现不可逆的杯状细胞化生。杯状细胞的变化与剂量相关；在第16天给予0.1毫克/100克体重或更低剂量时，不到一半的动物出现轻微或中度杯状细胞化生，而给予0.2至0.5毫克/100克体重剂量治疗的动物中，84%出现杯状细胞化生病变，其中一半以上被认为是严重的。经弹性蛋白酶处理的仓鼠上皮中杯状细胞的百分比（32.5）显著高于未暴露的对照组（12.2）和经盐水处理的对照组（18.7）（P小于0.005）。在弹性蛋白酶处理后6个月和12个月检查的所有仓鼠均显示出该病变。这些变化的发病机制尚不清楚，但有可能支气管变化是由于内源性蛋白酶 - 抗蛋白酶系统紊乱所致。这些发现提示了一种假说，即在适当情况下，人类单次肺部损伤可能导致永久性肺损伤，表现出慢性支气管炎和全腺泡型肺气肿的解剖学病变。
