Subchronic pulmonary inflammation and fibrosis induced by silica in rats are attenuated by amiodarone
Subchronic pulmonary inflammation and fibrosis induced by silica in rats are attenuated by amiodarone
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DOI：
10.3109/01902149609074021
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发表时间：
1996-01-01
影响因子：
1.7
通讯作者：
Reasor, MJ
中科院分区：
文献类型：
--
作者：
Blake, TL;Dimatteo, M;Reasor, MJ
先前的一项研究表明，大鼠中二氧化硅诱导的肺损伤的急性期可通过伴随给予胺碘酮（一种抑制肺中磷脂酶活性的阳离子两亲性药物）来减轻。本研究的目的是确定胺碘酮持续给药是否可以抑制亚慢性二氧化硅诱导的肺损伤和纤维化。向雄性Fischer-344大鼠施用胺碘酮（150 mg/kg; p.o.，5天/周），持续14天，然后向气管内滴注二氧化硅（100 mg/kg）。胺碘酮治疗持续60天。以支气管肺泡灌洗液指标评价肺损伤，以肺组织羟脯氨酸含量和胶原三色染色评价肺纤维化。在支气管肺泡灌洗液中，胺碘酮治疗导致二氧化硅诱导的白蛋白水平升高、乳酸脱氢酶活性、β-葡萄糖醛酸酶活性和中性粒细胞内流显著降低。胺碘酮治疗导致二氧化硅诱导的肺重量和羟脯氨酸水平增加显著降低;胺碘酮治疗导致的纤维化减少在组织学上得到证实。这些结果表明，在大鼠中由二氧化硅诱导的亚慢性肺部炎症和纤维化可以通过伴随给予胺碘酮来减弱。
A previous study demonstrated that the acute phase of silica-induced lung injury in rats can be attenuated by concomitant administration of amiodarone, a cationic amphiphilic drug that inhibits phospholipase activity in the lungs. The purpose of the present study was to determine whether continued amiodarone administration could inhibit subchronic silica-induced lung injury and fibrosis. Male Fischer-344 rats were administered amiodarone (150 mg/kg; p.o., 5 days/week) for 14 days and were then, instilled with silica (100 mg/kg) intratracheally. Amiodarone treatment then continued for 60 days. Injury was evaluated by parameters in bronchoalveolar lavage fluid and fibrosis was assessed by lung hydroxyproline content and trichrome staining of collagen. Within the bronchoalveolar lavage fluid, amiodarone treatment resulted in significant decreases in silica-induced elevations in albumin levels, lactate dehydrogenase ac tivity, beta-glucuronidase activity, and neutrophil influx. Amiodarone treatment resulted in significant reductions in silica-induced increases in lung weight and hydroxyproline levels; the diminution of fibrosis due to amiodarone treatment was confirmed histologically. These results indicate that subchronic pulmonary inflammation and fibrosis induced by silica in the rat can be attenuated by the concomitant administration of amiodarone.