J Korean Med Sci. 2016;31(9):1419-25.
Metformin Reduces Bleomycin-induced Pulmonary Fibrosis in Mice.
제1저자 최선미, 장안희 · 교신저자 김영환
소속 (3)
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University College of Medicine, Seoul National University Hospital, Seoul, Korea.
- Department of Pathology, Seoul National University Hospital, Seoul, Korea.
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University College of Medicine, Seoul National University Hospital, Seoul, Korea. ywkim@snu.ac.kr.
Abstract
Metformin has anti-inflammatory and anti-fibrotic effects. We investigated whether metformin has an inhibitory effect on bleomycin (BLM)-induced pulmonary fibrosis in a murine model. A total of 62 mice were divided into 5 groups: control, metformin (100 mg/kg), BLM, and BLM with metformin (50 mg/kg or 100 mg/kg). Metformin was administered to the mice orally once a day from day 1. We sacrificed half of the mice on day 10 and collected the bronchoalveolar lavage fluid (BALF) from their left lungs. The remaining mice were sacrificed and analyzed on day 21. The right lungs were harvested for histological analyses. The messenger RNA (mRNA) levels of epithelial-mesenchymal transition markers were determined via analysis of the harvested lungs on day 21. The mice treated with BLM and metformin (50 mg/kg or 100 mg/kg) showed significantly lower levels of inflammatory cells in the BALF compared with the BLM-only mice on days 10 and 21. The histological examination revealed that the metformin treatment led to a greater reduction in inflammation than the treatment with BLM alone. The mRNA levels of collagen, collagen-1, procollagen, fibronectin, and transforming growth factor-β in the metformin-treated mice were lower than those in the BLM-only mice on day 21, although statistical significance was observed only in the case of procollagen due to the small number of live mice in the BLM-only group. Additionally, treatment with metformin reduced fibrosis to a greater extent than treatment with BLM alone. Metformin suppresses the inflammatory and fibrotic processes of BLM-induced pulmonary fibrosis in a murine model.
Keywords
BleomycinMetforminMicePulmonary Fibrosis
Figures
그림 출처: PubMed Central 공개 논문 (PMC4974183)
Conflict of interest statement
DISCLOSURE: The authors have no potential conflicts of interest to disclose.
그 밖의 정보
- 출판 형태
- Journal Article
- 저널
- Journal of Korean medical science · eISSN 1598-6357
- MeSH
- Animals · Bleomycin / toxicity · Bronchoalveolar Lavage Fluid / chemistry · Collagen Type I / genetics / metabolism · Dose-Response Relationship, Drug · Female · Fibronectins / genetics / metabolism · Lung / pathology · Metformin / therapeutic use · Mice · Mice, Inbred C57BL · Pulmonary Fibrosis / chemically induced / prevention & control · RNA, Messenger / metabolism · Tumor Necrosis Factor-alpha / metabolism
- Substances
- Collagen Type I · Fibronectins · RNA, Messenger · Tumor Necrosis Factor-alpha · Bleomycin · Metformin
- 참고문헌
- 16편