Oral N-acetylcysteine attenuates elastase-induced pulmonary emphysema in rats
Oral N-acetylcysteine attenuates elastase-induced pulmonary emphysema in rats
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DOI：
10.1378/chest.125.4.1500
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发表时间：
2004-04-01
期刊：
影响因子：
9.6
通讯作者：
González-Mangado, N
中科院分区：
文献类型：
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作者：
Rubio, ML;Martin-Mosquero, C;González-Mangado, N
研究目的：探讨抗氧化剂n -乙酰半胱氨酸（NAC）对弹性酶致大鼠肺气肿的影响。材料与方法：Wistar大鼠（72只）经气管灌注75iu弹性蛋白酶或生理盐水。每组18只大鼠从诱导病变前2天开始注射抗氧化剂NAC，直至注射后2、8、28天处死。通过测量左肺胶原蛋白含量、组织病理学评估（即平均肺泡内表面积（AIA）和平均线性截距测量）和肺功能来评估治疗效果。结果：弹性酶注射28 d后，NAC处理大鼠与弹性酶单独处理大鼠相比，病变明显减弱，包括：平均（+/- SEM）胶原含量正常化（分别为1.23 +/- 0.09和1.51 +/- 0.10 mg /左肺，p < 0.05）；部分抑制平均AIA（分别为14,860 +/- 1,135和19,622 +/- 1,294）；P < 0.05)，平均线性截距分别为108.8 +/- 3.7和123.0 +/- 4.2,P < 0.05)；呼气流量增加和改善（分别为27.8 +/- 1.2 vs 23.4 +/- 1.3 mL/s, p < 0.05）。NAC不能避免弹性酶加NAC组顺应性增高。结论：NAC能够减轻弹性蛋白酶诱导的大鼠损伤，与解剖、病理和功能研究结果一致，这与先前的数据支持氧化损伤可能促进弹性蛋白酶诱导的肺气肿发展的观点一致。
Study objective: To study the effect of the antioxidant N-acetylcysteine (NAC) in the development of elastase-induced emphysema in rats.Materials and methods: Wistar rats (n = 72) were orotracheally instilled with 75 IU elastase or saline solution. Eighteen rats from each group received the antioxidant NAC from 2 days before induction of the lesion until they were killed 2, 8, and 28 days after instillation. The effects of treatment were assessed by measuring collagen content for the left lung, a histopathology evaluation (ie, mean alveolar internal surface area (AIA) and mean linear intercept measurement), and lung function.Results: Twenty-eight days after elastase instillation, rats treated with NAC showed significant attenuation of the lesion in comparison with rats treated only with elastase, including the following: normalization of mean (+/- SEM) collagen content (1.23 +/- 0.09 vs 1.51 +/- 0.10 mg per left lung, respectively; p < 0.05); partial inhibition of mean AIA (14,860 +/- 1,135 vs 19,622 +/- 1,294 mum(2), respectively; p < 0.05) and mean linear intercept (108.8 +/- 3.7 vs 123.0 +/- 4.2 mum, respectively; p < 0.05); and increases and improvement in expiratory flows (27.8 +/- 1.2 vs 23.4 +/- 1.3 mL/s, respectively; p < 0.05). NAC was not able to avoid the compliance increase in the elastase-plus-NAC group.Conclusion: Consistent with the results of anatomic, pathologic, and functional studies, NAC is able to attenuate the lesions induced by elastase in rats, which is in accordance with previous data supporting the idea that oxidant injury could contribute to the development of elastase-induced emphysema.