不同剂量博莱霉素诱导小鼠肺纤维化的差异及动态变化

发布时间：2019-06-15 01:00

【摘要】：目的探讨博来霉素诱导小鼠肺纤维化最佳剂量和方法。方法 126只8周龄雄性ICR小鼠,随机分成一次性大剂量模型和多次小剂量模型。一次性大剂量模型分为200 mg/(kg.bw)BLM组、150 mg/(kg.bw)BLM组、100 mg/(kg.bw)BLM组及阴性对照组(DN组),每组18只,分别经尾静脉一次性注射BLM 200、150、100mg/(kg.bw)及生理盐水10 mL/(kg.bw),各组分别于第7、14、21天各处死6只。多次小剂量模型分为每日10 mg/(kg.bw)BLM组及阴性对照组(N组),分别经尾静脉注射BLM 10 mg/(kg.bw)及生理盐水10 mL/(kg.bw),每天1次,连续注射14 d,两组分别于第14、21、28天各处死6只。留取肺组织,观察肺组织病理改变,检测Ⅲ型胶原的含量,观察小鼠体重及生存率。结果①在一次性大剂量模型中,BLM各剂量组肺泡炎症评分及肺纤维化评分与正常组相比,除100 mg/(kg.bw)BLM组和150 mg/(kg.bw)BLM组在第7天的模型差异无显著性外(P0.05),其余各组差异均有显著性(P0.05);各个剂量组Ⅲ型胶原的表达面积与正常组相比,除100 mg/(kg.bw)BLM组在第7天的模型差异无显著性外(P0.05),其余各组均较正常组高(P0.05),各个剂量组分别在第21天达到高峰,以200 mg/(kg.bw)BLM组第21天组Ⅲ型胶原的表达面积最高;该模型小鼠各剂量组死亡率为0。②在多次小剂量模型中,各组的肺泡炎症与肺纤维化程度与正常组相比差异均有显著性(P0.05);各组Ⅲ型胶原的表达也均高于正常组(P0.05),且随着时间的延长呈进行性增加,在第28天达到高峰;该模型小鼠共死亡11只,死亡率为30.56%。结论在本实验中,以尾静脉一次性注射BLM 200 mg/(kg.bw)后第21天诱导建立的ICR小鼠肺纤维化模型成模最好,其小鼠死亡率低,操作简单,有效安全方便的特点使之有希望成为一种复制肺纤维化的理想模型。
[Abstract]:Objective to investigate the best dose and method of bleomycin induced pulmonary fibrosis in mice. Methods 126 8-week-old male ICR mice were randomly divided into one-time high dose model and multiple low dose model. The one-time high dose model was divided into two groups: 200 mg/ (kg.bw) BLM group, 150 mg/ (kg.bw) BLM group, 100mg/ (kg.bw) BLM group and negative control group (DN group) with 18 rats in each group. BLM 200150100mg/ (kg.bw) and saline 10 mL/ (kg.bw) were injected intravenously through tail vein. 6 rats in each group died on the 7th, 14th and 21st day, respectively. The low dose model was divided into 10 mg/ (kg.bw) BLM group and negative control group (N group). BLM 10 mg/ (kg.bw) and saline 10 mL/ (kg.bw) were injected intravenously once a day for 14 days. 6 rats in the two groups died on the 14th, 21st and 28th day, respectively. The lung tissue was taken, the pathological changes of lung tissue were observed, the content of type III collagen was detected, and the body weight and survival rate of mice were observed. Results 1 in the one-off high dose model, compared with the normal group, the alveolar inflammation score and pulmonary fibrosis score of each dose group of BLM were significantly different from those of the normal group, except for the model of 100 mg/ (kg.bw) BLM group and 150 mg/ (kg.bw) BLM group on the 7th day (P 0.05). Compared with the normal group, the expression area of type III collagen in each dose group was not significantly different from that in the normal group on the 7th day (P 0.05). The expression area of type III collagen in each dose group reached the peak on the 21st day, and the expression area of type III collagen in the 200 mg/ (kg.bw) BLM group was the highest on the 21st day. The mortality of each dose group was 0.2 in multiple low dose models, the degree of alveolar inflammation and pulmonary fibrosis in each group was significantly different from that in the normal group (P 0.05), and the expression of type III collagen in each group was also higher than that in the normal group (P 0.05), and increased gradually with the prolongation of time and reached the peak on the 28th day. 11 mice died in this model, the mortality rate was 30.56%. Conclusion the model of pulmonary fibrosis in ICR mice induced by tail vein injection of BLM 200 mg/ (kg.bw) on the 21st day is the best. The characteristics of low mortality, simple operation, effective, safe and convenient make it an ideal model for replication of pulmonary fibrosis.
【作者单位】：中南大学湘雅医院;
【基金】：湖南省科研条件创新专项基金资助项目(2010TD2013)
【分类号】：R563.9

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