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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。
Objective: To observe the effect of endogenous peroxynitrite anion (ONOO ~ -) on bleomycin A 5 -induced lung injury and pulmonary fibrosis in rats. METHODS: Lung injury and pulmonary fibrosis were assessed by measuring the level of pulmonary lipid peroxidation and observing lung histological changes, including changes in Sirius red staining of type I and type III collagen using a polarizing microscope. Tyrosine immunohistochemistry to determine the expression of peroxynitrite. Results: On the 14th day after intratracheal injections of bleomycin A5, (1) elevated pulmonary lipid peroxidation levels were observed; alveolar wall thickening and pulmonary interstitial macrophage infiltration were observed and there were fibroblasts and fibroblasts nearby Increased type Ⅰ, Ⅲ collagen. (2) ONOO ~ - overexpression in alveolar epithelial cells and pulmonary interstitial cells. (3) The induction of nitric oxide synthase (iNOS) inhibitor aminoguanidine alleviated the above changes. CONCLUSION: Endotoxic ONOO ~ - mediates the lung toxicity of BLM-A_5. The therapeutic effect of aminoguanidine on lung injury and pulmonary fibrosis is partly achieved by reducing the formation of endogenous ONOO ~ -.