正常大鼠吸入一氧化氮毒副作用的实验观察

Experimental Study on Toxicity of Nitric Oxide Inhalation in Rats

目的：观察正常大鼠延时吸入低浓度一氧化氮（ＮＯ）的毒副作用。方法：将大鼠置于ＮＯ吸入系统，分别吸入２０ｐｐｍ（１ｐｐｍ＝１／１０６）、４０ｐｐｍ、８０ｐｐｍ浓度ＮＯ，８ｈ／ｄ，对照组吸入自然空气，３周后，观察肺动脉压、颈动脉压、高铁血红蛋白含量和血气变化。取肺组织做光、电镜病理学检查。结果：各组大鼠高铁血红蛋白含量及血气指标均无明显差异。吸入８０ｐｐｍＮＯ的大鼠肺系数明显增加。吸入２０ｐｐｍＮＯ后，光、电镜下肺组织结构无异常；吸入４０ｐｐｍＮＯ后，光镜下偶见肺血管充血，轻度间质水肿；电镜下，血管内皮细胞下出现少量空泡；吸入８０ｐｐｍＮＯ后，除可见上述病理改变外，还可见局灶性肺泡内少量红细胞渗出、肺泡内水肿、肺间质炎。电镜下，可见少数Ｉ型和ＩＩ型肺泡上皮细胞线粒体嵴溶解、模糊，内质网扩张。结论：延长吸入时间，吸入２０ｐｐｍＮＯ无明显毒副作用。而吸入４０ｐｐｍ和８０ｐｐｍＮＯ可分别导致轻度和中度可逆性肺损伤。

Objective:To observe the toxicity of long time inhalation of NO in rats for clinical application of NO with safety. Methods:Male Wistar rats were exposed to 20 ppm( n =6),40 ppm( n =6),and 80 ppm( n =7) of NO,respectively for 8 hours a day with special NO exposure system.The rats exposed to cabinet air served as control ( n =6).After three weeks exposure,the hemodynamic parameters,methemoglobin,arterial blood gases and lung index were measured;the pathological changes of lung tissue were investigated by light and transmission electron microscopy. Results:No statistical difference of methemoglobin and arterial blood gases were showed among the experimental groups and control group.The lung index was markedly increased in 80 ppm NO exposed group as compared with control (0 62±0 06 vs. 0 53±0 02; p <0 01).Exposure of rats to 20 ppm NO brought about undetectable histopathologic changes in lung.Mild congestion,lung interstitial edema and vacuolization inside the vascular endothelial cells were occasionally found in 40 ppm NO exposed rats.Besides the above mentioned histological changes,mild interstitial inflammation,alveolar edema,the trace extravasation of fibrin into the alveolar space,mitochondrial crista lysis and endoplasmic reticulum dilation in type I and II pneumocytes also existed in 80 ppm NO exposed rats. Conclusions:The fact that inhalation of 40 ppm or 80 ppm NO could result in slightly or moderately reversible lung damage in rats suggests the minimal effective NO dosage should be recommended in long term clinical application.