Braga P C, Piatti G, Limoli A, Dal Sasso M, Maci S
Centre for Respiratory Pharmacology, Faculty of Medicine, University of Milan, Italy.
Drugs Exp Clin Res. 1995;21(2):51-7.
The instillation of elastase into airways is a widely adopted experimental method to quickly produce emphysematous lesions that mimic human disease anatomically and physiologically. Experiments were undertaken to determine whether of not neltenexine, a new drug active on surfactant production, would diminish the severity of this disease. Anaesthetized rats were instilled tracheally with porcine pancreatic elastase (46 U/mg) dissolved in saline, in a single instillation of 0.33 mg/100 microliters. Neltenexine was administered in one experiment at the dose of 25 mg/kg i.p. daily for 30 days. In a second test, neltenexine was given at the same dose six days before the elastase instillation and then by the same schedule as in the first experiment; this was done in search of a possible preventive action. At the end of the treatment, lungs were removed and fixed, and slices were dehydrated, critically point dried, coated with gold and observed by scanning electron microscopy (SEM). Rats that were both pretreated and treated with neltenexine showed a significant reduction in the alveolar deformation induced by elastase. There were no differences between pretreated and treated animals. These experimental findings suggest that neltenexine might prove to be useful for preventing pulmonary emphysema. Biochemical studies in man are needed to confirm the clinical application of neltenexine.
将弹性蛋白酶滴入气道是一种广泛采用的实验方法，可快速产生在解剖学和生理学上模拟人类疾病的肺气肿病变。开展实验以确定一种对表面活性剂产生有活性的新药奈替西尼是否会减轻这种疾病的严重程度。将麻醉的大鼠经气管滴入溶解于盐水中的猪胰弹性蛋白酶（46 U/mg），单次滴入剂量为0.33 mg/100微升。在一项实验中，奈替西尼按25 mg/kg的剂量腹腔注射，每日一次，共30天。在第二项试验中，在滴入弹性蛋白酶前6天给予奈替西尼相同剂量，然后按与第一项实验相同的方案给药；这样做是为了寻找可能的预防作用。在治疗结束时，取出肺脏并固定，切片进行脱水、临界点干燥、喷金，然后用扫描电子显微镜（SEM）观察。预先给药和给药治疗的大鼠显示出弹性蛋白酶诱导的肺泡变形显著减少。预先给药和给药治疗的动物之间没有差异。这些实验结果表明，奈替西尼可能被证明对预防肺气肿有用。需要在人体进行生化研究以证实奈替西尼的临床应用。
