Establishment And Evaluation Of The Model Of Bleomycin-induced Pulmonary Fibrosis In Rats With Tracheal Spraying Administertion

Purpose: Idiopathic pulmonary fibrosis is characterized by radiographically evidentinterstitial infiltrates predominantly affecting the lung bases and by progressive dyspneaand worsening of pulmonary function. It is a chronic disease of the lung parenchyma thatleads to diffuse scarring and end-stage tissue fibrosis. No therapy has been clearly shownto prolong survival, and the mortality rate is high. To stablish and evaluate a stable,repeatable, and high similar animal model of pulmonary fibrosis is important for us. Therewill have a great significance for us to study of idiopathic pulmonary interstitial fibrosisand diffuse fatal interstitial lung disease mechanism, for futher study of prevention,diagnosis and treatment of pulmonary fibrosis disease or diagnostic reagents, for futhersignificance to the development of medical technology and improving of the living level ofpatients.Method: The rats were administered with tracheal spraying bleomycin, and weresacrificed after treatment at different weeks, observed the daily status of rats,body weightchange,determinated the weight of lung and pulmonary coefficient, hydroxyproline(HYP)content,and their lungs were harvested for histological studies, pathological section of lungtissue were taken for morphological evaluation after staining of HE, Masson.By comparingthe pulmonary morphological changes in different dosage and execution time to explorethe best fibrosis model method.Result：(1) The spirit and appetite status wer good of saline group and blank control groupafter administration. But the model groups all appeared independent tremor, ataxia, slience,burnout, and slμggish states. Moreover, the high dose group’s hair became red. Five dayslater, those symptoms were relief. But in two weeks, the rats became dull, slμggish and soon.(2) The weight of saline group was unchanged basically within three days afteradministration. Three days later, the weight increased daily. The weight of model grouphad a sharp decline, increased daily in five days later.(3) The lung coefficient of model rats increased gradually with prolonging themodeling time. There was no obvious change between saline group and blank controlgroup, and compared with saline group and blank control group(P＜0.05). (4) The optimal condition for HYP content detection in lung tissue of rats consisted of7.5M HCL hydrolyze16h at110℃，oxidative for10min at room temperature anddevelopingfor25min at60℃.The sensitivity was0.067μg/mL.The recovery and averageCV of this method were88.85%~110.88%and4.7%~6.6%，respectively. With this method,we found that in the study of bleomycin induced lung fibrosis of rats，the HYP content ofmodel group was higher obviously than control group. However, the HYP content of salinegroup also increased.(5) In a word, from the observation of rat lung tissue pathology, we draw that4U/kgof two days administration of model group after four weeks can produce significantfibrosis symptoms and the fibrosis symptoms more uniform distribution, moreover, theupper lobe of the lung is more obvious than the middle and lower lobe.Conclusion: The model of bleomycin-induced pulmonary fibrosis in rats withtracheal spraying administertion could be established successfully. However, the successrate of the model is no high, how to prepare stable, feasible, high similarity and successrate of animal model will be our direction in the future.