Rat and hamster species differences in susceptibility to elastase-induced pulmonary emphysema relate to differences in elastase inhibitory capacity
Rat and hamster species differences in susceptibility to elastase-induced pulmonary emphysema relate to differences in elastase inhibitory capacity
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DOI：
10.1152/ajpregu.00343.2007
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发表时间：
2007-09-01
影响因子：
2.8
通讯作者：
Lisboa, Carmen
中科院分区：
文献类型：
--
作者：
Borzone, Gisella;Liberona, Leonel;Lisboa, Carmen
叙利亚金仓鼠在气管内注射单次弹性蛋白酶后会出现严重的肺气肿，而斯普拉格-道利大鼠在每公斤体重相同剂量的情况下会出现轻度肺气肿。我们推测，与仓鼠相比，大鼠血清中高水平的 α1-抗胰蛋白酶可预防大鼠严重肺气肿的发生，而仓鼠具有较高的肺弹性蛋白酶抑制能力 (EIC)。为了探索这种可能性，我们通过每周用三个相似剂量的弹性蛋白酶治疗大鼠来挑战它们的抗蛋白酶系统。治疗四个月后，我们评估了大鼠肺部的组织学、体积和弹性特性的变化，并将其与接受单剂量弹性蛋白酶的仓鼠进行了比较。我们还测量了对照大鼠和仓鼠的血清 α1-抗胰蛋白酶水平以及血清和肺 EIC。结果显示，与大鼠相比，血清和肺 EIC 减少 40%（P < 0.001），仓鼠肺上叶肺大泡形成，严重的微观肺气肿，肺容积增加四倍（P < 0.01），肺通气压力容积曲线的顺应性指数常数 k 增加三倍（P < 0.01）。相比之下，大鼠出现轻度肺气肿，体积仅增加 50%（P < 0.05），常数 k 增加 60%（P < 0.01）。总之，血清和肺 EIC 不同的两个物种在弹性蛋白酶作用后肺气肿的发展方面表现出显着差异。尽管接受了三剂弹性蛋白酶，但高 EIC 的大鼠表现出的形态和生理参数的紊乱明显少于接受单剂量 EIC 的仓鼠。
Syrian Golden hamsters develop severe emphysema after a single intratracheal dose of elastase, whereas Sprague- Dawley rats exhibit mild emphysema with the same dose per kilogram body weight. We hypothesized that the development of severe emphysema is prevented in rats by the high serum level of alpha 1- antitrypsin reported in rats, compared with hamsters, which provides for a high lung elastase inhibitory capacity ( EIC). To explore this possibility, we challenged the antiprotease system of the rats by treating them with three similar weekly doses of elastase. Four months after treatment, we evaluated changes in histology, volume, and elastic properties of rat lungs and compared them with those of hamsters receiving a single dose of elastase. We also measured serum alpha 1- antitrypsin levels and serum and lung EIC in control rats and hamsters. Results showed that, in association with 40% less serum and lung EIC compared with rats ( P < 0.001), hamster lungs had upperlobe bullae formation, severe microscopic emphysema, a fourfold increase in lung volume ( P < 0.01) and a threefold increase in constant k, an index of compliance, of the lung deflation pressurevolume curve ( P < 0.01). In contrast, rats developed mild emphysema, with only 50% increase in volume ( P < 0.05) and 60% increase in constant k ( P < 0.01). In conclusion, two species that differ in serum and lung EIC exhibit significant differences in emphysema development after elastase. Rats with high EIC, despite receiving three doses of elastase, showed significantly less derangement of morphological and physiological parameters than hamsters with low EIC receiving a single dose.