Comparison and evaluation of different doses of bleomycin-induced pulmonary fibrosis models in mice and rats
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1. Co-construction Collaborative Innovation Center for Chinese Medicine and Respiratory Diseases by Henan Education Ministry of P. R. , Henan University of Chinese Medicine, Zhengzhou 450046, China. 2. Henan Key Laboratory of Chinese Medicine for Respiratory Disease, Henan University of Chinese Medicine, Zhengzhou 450046

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    Abstract:

    Objective To determine the appropriate dose of bleomycin to induce pulmonary fibrosis in rat and mice models via a single intratracheal instillation and to compare model characteristics. Methods Thirty SD rats were randomly divided into blank group, bleomycin low-dose group (3 mg/ kg, BL-L group), bleomycin high-dose group (5 mg/ kg, BL-H group), 10 in each group, and 30 C57BL/6J mice were grouped as above. The animals’ general condition and body weight changes were observed. The tidal volume (TV), minute ventilation (MV), and 50% tidal volume expiratory flow (EF50) of rats and mice were measured with an animal lung function instrument. HE and Masson’s staining were used to observe histological changes to the lung tissues. Lung collagen content was measured with a hydroxyproline (HYP) kit. Results In the BL-L and BL-H groups, the survival rates of C57BL/6J mice were 70% and 80% and those of SD rats were 70% and 50%, respectively. From day 7, there was a significant decrease in the body weight of C57BL/6J mice in the BL-H group (P< 0. 05, P< 0. 01) and SD rats in the BL-L and BL-H groups (P< 0.01). Compared with the blank group, TV was decreased in SD rats in both dose groups (P < 0. 01) on day 10, but no significant change was observed in C57BL/6J mice. On day 21, lung function TV and MV were significantly decreased in the BL-L group rats (P< 0. 05, P< 0. 01); TV was significantly decreased in the BL-H group rats (P< 0. 01); and TV, MV, and EF50 were significantly decreased in C57BL/6J mice in both dose groups (P< 0. 05, P< 0. 01). In the lung tissues of C57BL/6J mice and SD rats in the BL-L and BL-H groups on day 21, inflammatory infiltration and fibrous cords appeared, alveolitis and fibrosis degree scores were significantly increased (P< 0. 05, P< 0. 01), and HYP levels were significantly increased (P< 0. 05, P< 0. 01). Conclusions Both 3 mg/ kg and 5 mg/ kg bleomycin induced pulmonary fibrosis models in rats and mice. Based on survival rate, lung function, lung pathology, and other indicators, the optimal dose for C57BL/6J mice was 5 mg/ kg and that for SD rats was 3 mg/ kg.

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  • Received:June 14,2022
  • Online: October 17,2023
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