Comparison of pulmonary fibrosis rat models induced by different dosed of bleomycin
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1. Henan University of Chinese Medicine, Co-Construction Collaborative Innovation Center for Chinese Medicine and Respiratory Diseases by Henan & Education Ministry of PR, Henan Key Laboratory of Chinese Medicine for Respiratory Disease, Zhengzhou 450046, China. 2. Henan University of Chinese Medicine, Academy of Chinese Medical Sciences, Zhengzhou 450046. 3. the First Affiliated Hospital, Henan University of Chinese Medicine, Zhengzhou 450000

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R-33

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    Abstract:

    Objective To compare the success rate and stability of rat pulmonary fibrosis (PF) models induced by intratracheal instillation of different doses of bleomycin (BLM). Methods One hundred and fifty Sprague Dawley rats were divided randomly into control, low-dose BLM 3 mg/kg (BL-L), and high-dose BLM 5 mg/kg (BL-H) groups. General status, mortality, and weight changes were observed, and the lung inspiratory capacity (IC), vital capacity (VC), chord compliance (Cchord), and dynamic compliance (Cdyn) were detected on days 28, 42, 56, and 84. Lung coefficients were recorded and pathological changes in lung tissue were observed by hematoxylin and eosin and Masson staining. The lung hydroxyproline (HYP) content was detected and collagen type III (COL III) was detected by immunohistochemistry. Results The mortality rates in the BL-L and BL-H groups were 20% and 28%, respectively. Body weight was significantly lower in the BL-L group compared with the control group on days 0~56, and weight recovery after day 56. Body weight was significantly lower in the BL-H group compared with the control and BL-L groups from days 0~56 (P<0.01). Regarding lung function, IC, VC, Cchord, and Cdyn were significantly lower in the BL-L group compared with the control group on day 28 (P<0.01, P<0.05), and IC and Cdyn were significantly lower in the BL-H group (P< 0.01). IC, VC, and Cchord were significantly decreased in the BL-L group on day 42 (P<0.01, P<0.05), while IC, VC, Cchord, and Cdyn were significantly decreased in the BL-H group (P<0.01, P<0.05), and IC, VC, and Cchord were significantly lower compared with in the BL-L group (P<0.01). Cchord was significantly lower in the BL-H group compared with the control and BL-L groups on day 56 (P<0.01). The lung coefficients on day 28 were significantly higher in the BL-L and BL-H groups compared with the control group (P<0.01), and were significantly higher in the BL-H group from days 42~56 compared with the BL-L and control groups (P<0.01). Regarding lung histopathology and immunohistochemistry, inflammatory infiltration, fibrotic streaks, and COL III expression were observed in the BL-L group from days 28~56, and almost complete disappearance of the fibrotic lesions on day 84. In contrast, fibrotic lesions could be observed from days 28~84 in the BL-H group, with significantly elevated COL III expression compared with the control group (P<0.01). The HYP content was significantly higher in the BL-L group compared with the control group from days 28~42 (P<0.05, P<0.01), and then gradually decreased, and the HYP content was significantly higher in the BL-H group than in the control group from days 28~84 (P<0.01). Conclusions Both 3 and 5 mg/kg BLM can successfully induce PF rat models. Rats treated with 3 mg/kg BLM developed fibrosis on day 28, which lasted until day 42 and then gradually recovered. Rats treated with 5 mg/kg BLM developed fibrosis on day 28, and the degree of fibrosis was more severe with the higher compared with the lower dose, with stablefibrotic lesions up to day 56 and moderate-to-severe fibrosis still present in half of the rats until day 84.

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History
  • Received:June 11,2024
  • Online: November 19,2024
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