Role of endogenous peroxynitrite in pulmonary injury and fibrosis induced by bleomycin A_5 in rats  

内源性过氧亚硝基阴离子在博莱霉素A_5诱发大鼠肺损伤和肺纤维化中的作用(英文)

作　　者：陈晓玲[1] 李文斌[1] 周爱民[1] 艾洁[1] 黄善生[1] 

机构地区：[1]河北医科大学基础医学研究所病生研究室

出　　处：《Acta Pharmacologica Sinica》2003年第7期75-80,105,共7页中国药理学报（英文版）

摘　　要：AIM: To observe the role of endogenous peroxynitrite （ONOO^-） in pulmonary injury and fibrosis induced by bleomycin A₅ （BLM-A₅） in rats. METHODS: Pulmonary injury and fibrosis of rats were evaluated by testing the level of lipid peroxides （LPO） in out-going pulmonary blood （OPB）, and by observing histological changes, including type Ⅲ and type Ⅰ collagen changes in lung which were examined with Sirius red staining under polarized light. The peroxynitrite expression was detected by immunohistochemistry for nitrotyrosine （NT）, a marker of the peroxynitrite production. RESULTS: （1） The level of LPO was elevated in OPB of rats on d 14 after intratracheal administration of BLM-A₅. Thickened alveolar wall and macrophage infiltration were seen, and fibroblasts were near by the interstitial macrophages. Increased amounts of type Ⅲ collagen and type Ⅰ collagen were deposited in disoriented fashion. （2） High expression of ONOO^- was detected in alveolar epithelial cells and pulmonary interstitial macrophages. （3） Th above changes were reduced by aminoguanidine （AG）, an inhibitor of nitric oxide synthase （iNOS）. CONCLUSION: Endogenous ONOO^- mediated BLM-A₅-induced pulmonary toxicity. The therapeutic potential of AG for pulmonary injury and fibrosis was realized partly by reducing ONOO^- formation.目的:观察内源性过氧亚硝基阴离子(ONOO^-)在博莱霉素A_5诱发大鼠肺损伤和肺纤维化中的作用。方法:通过测定出肺血脂质过氧化物水平和观察肺组织学变化(包括用偏振光显微镜观察天狼猩红染色的Ⅰ、Ⅲ型胶原的变化)来判断肺损伤和肺纤维化;用硝基酪氨酸的免疫组化判断过氧亚硝基阴离子的表达。结果:气管内给予博莱霉素A_5第14天观察到(1)出肺血脂质过氧化物含量升高;肺泡壁增厚,肺间质巨噬细胞浸润,且其邻近有成纤维细胞及增多的Ⅰ、Ⅲ型胶原。(2)肺泡上皮细胞和肺间质细胞内ONOO^-高表达。(3)诱导型一氧化氮合酶(iNOS)抑制剂氨基胍减轻上述变化。结论:内源性ONOO^-介导BLM-A_5的肺毒性作用;氨基胍对肺损伤和肺纤维化的治疗部分是通过减少内源性ONOO^-的形成实现的。

关 键 词：peroxynitrous acid BLEOMYCIN TOXICITY pulmonary fibrosis GUANIDINES 

分 类 号：R9[医药卫生—药学]