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目的：应用苯肼建立小鼠急性溶血性贫血的方法已经成熟，但用苯肼建立慢性溶血性贫血模型尚未见报道。本研究试图应用苯肼口服法建立慢性溶血性贫血动物模型并探索最适建模的苯肼浓度。方法：42 只C57BL/6小鼠随机分为6 组，通过口服不同浓度的苯肼溶液，于口服后的第0，1，2，3，4，5，6 周目内眦采集小鼠外周血检测，记录相关指标变化，比较各组之间的差异，筛选出最佳慢性溶血效果的给药浓度。结果：口服苯肼溶液浓度在250 mg/L以下时C57BL/6小鼠没有出现明显的贫血状态，当浓度调至250 mg/L-350 mg/L时可使C57BL/6 小鼠在5-7 周内出现溶血性贫血症状，各组小鼠的皮肤和粘膜颜色苍白，外周血红细胞数量、血红蛋白含量、红细胞压积降低，网织红细胞比例增高。但是当浓度达到350 mg/L 时小鼠贫血情况过重且达不到慢性贫血的要求。当浓度为300 mg/L时小鼠各项血液指标平稳下降。结论：本实验建立了一种新的小鼠慢性贫血模型，且通过实验发现小鼠口服苯肼致慢性贫血的最佳浓度为300 mg/L。据我们所知，这是首次使用苯肼建立慢性贫血的动物模型，此模型对研究人类慢性贫血具有重要价值。

英文摘要:

Objective:The acute, but not chronic, mouse anemic model induced by phenylhydrazine has been established. The aim of this study is to establish a mouse chronic hemolytic anemia model using phenylhydrazine and to explore the best phenylhydrazine concentration for this chronic anemia mouse model.Methods:Forty-two C57BL/6 mice were randomly separated into 6 groups, and each group was orally fed with different concentrations of phenylhydrazine in drinking water. The peripheral blood cell indices after feeding with phenylhydrazine at week 0, 1, 2, 3, 4, 5, 6 were recorded, the change of the relevant parameters were examined, and the most appropriate concentration of phenylhydrazine was determined.Results:Mice didn't show obvious anemic phenotype when the concentration of phenylhydrazine in drinking water was below 250 mg/L. However, mice showed profound symptoms of hemolytic anemia around week 5 to 7 when the concentration of phenylhydrazine was between 250-350 mg/L, indicating a chronic anemia in animals was induced. When the concentration of phenylhydrazine reached 300 mg/L, mice committed weight loss, and pale skin and mucosa. Moreover, at the concentration of 300 mg/L, total red cell count, hemoglobin level and hematocrit were dramatically diseased, while the percentage of reticulocytes in blood and red cell distribution width were significantly increased, suggesting that 300 mg/L was the best concentration for induction of chronic anemia. Mice developed profound anemia in much short time (less than 5-7 weeks) when the concentrations of phenylhydrazine was more than 350 mg/L, which suggested a much stronger induction of anemia by oral ingestion of phenylhydrazine.Conclusion:A chronic mouse model of hemolytic anemia induced by phenylhydrazine is successfully established by oral uptake of phenylhydrazine in drinking water, and the best concentration of phenylhydrazine is around 300 mg/L. To our knowledge, this is the first time to show that phenylhydrazine can be used to develop chronic anemia models for the studies on certain human anemic diseases.

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