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| Therapeutic effect and Mechanism of 2-indolinone Derivatives on BLM-induced Pulmonary Fibrosis in Mice |
| JIANG Xing-wen, HAN Lin-xi |
| Department of Rehabilitation Medicine,Ankang Central Hospital,Ankang Shaanxi 725000 |
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Abstract 【Objective】To explore the therapeutic effect and related mechanism of 2-indolinone derivative (PMID) on bleomycin (BLM)-induced pulmonary fibrosis in mice. 【Methods】Forty SPF grade, 3-week-old male SD mice were randomly divided into the control group, the model group and the PMID low and high dose groups, with 10 mice in each group. After the pulmonary fibrosis model was successfully induced by BLM in model group and PMID low and high dose groups, mice in PMID low and high dose groups were given 5 mg/kg and 20 mg/kg PMID solution by gavage (twice·d, with an interval of 6~8 h) for 28 days. While mice in the control group and the model group were given the same amount of normal saline at the same time. After drug intervention, the histopathological changes and pulmonary fibrosis of mice in each group were observed by hematoxylin eosin (HE) staining and collagen fiber (Masson) staining, then the pulmonary fibrosis scores of mice were compared. The mRNA level of collagen Ⅲ in mouse lung was measured by real-time fluorescence quantitative PCR; Phosphatidylinositol 3-kinase (PI3K), p-PI3K, protein kinase B (AKT), p-AKT and hypoxia inducible factor-1α( HIF-1α) protein level were detected by Western blot. 【Results】Compared to the control group, the pulmonary fibrosis score, Collagen Ⅲ mRNA level, p-PI3K / PI3K, p-AKT / AKT and HIF-1α were higher in the model group, low dose PMID group and high dose PMID groups (P<0.05). While the pulmonary fibrosis score, Collagen Ⅲ mRNA level, p-PI3K / PI3K, p-AKT / AKT and HIF-1α of mice in low and high dose PMID groups were lower than those in the model group (P<0.05).In addition, the above index levels in the high-dose group were lower than those in the low-dose group (P<0.05). 【Conclusion】PMID can improve BLM-induced pulmonary fibrosis in mice, which may be related to the inhibition of PI3K / AKT / HIF-1α pathway activation and inhibition of collagen deposition.
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Received: 15 June 2022
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2022, Vol. 39 
