Rubio Maria L, Martin-Mosquero M Carmen, Ortega Mercedes, Peces-Barba German, González-Mangado Nicolás
Laboratorio Neumología Experimental, Servicio de Neumología, Fundación Jiménez Díaz, Universidad Autónoma, Madrid, Spain.
Chest. 2004 Apr;125(4):1500-6. doi: 10.1378/chest.125.4.1500.
To study the effect of the antioxidant N-acetylcysteine (NAC) in the development of elastase-induced emphysema in rats.
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.
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 micro m(2), respectively; p < 0.05) and mean linear intercept (108.8 +/- 3.7 vs 123.0 +/- 4.2 micro m, 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.
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.
研究抗氧化剂N - 乙酰半胱氨酸（NAC）对大鼠弹性蛋白酶诱导的肺气肿发展的影响。
将75 IU弹性蛋白酶或生理盐水经口气管内滴注到72只Wistar大鼠体内。每组18只大鼠从损伤诱导前2天开始接受抗氧化剂NAC治疗，直至滴注后2、8和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）以及肺功能来评估治疗效果。
弹性蛋白酶滴注28天后，与仅用弹性蛋白酶治疗的大鼠相比，接受NAC治疗的大鼠病变明显减轻，包括以下方面：平均（±标准误）胶原蛋白含量恢复正常（分别为每左肺1.23±0.09 vs 1.51±0.10 mg；p<0.05）；平均AIA部分受到抑制（分别为14,860±1,135 vs 19,622±1,294μm²；p<0.05）和平均线性截距（分别为108.8±3.7 vs 123.0±4.2μm；p<0.05）；呼气流量增加且改善（分别为27.8±1.2 vs 23.4±1.3 mL/s；p<0.05）。NAC未能避免弹性蛋白酶加NAC组的顺应性增加。
与解剖学、病理学和功能研究结果一致，NAC能够减轻大鼠弹性蛋白酶诱导的病变，这与先前支持氧化损伤可能导致弹性蛋白酶诱导的肺气肿发展这一观点的数据相符。
