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An inhibitory effect of tumor necrosis factor-alpha antagonist to gene expression in monocrotalineinduced pulmonary hypertensive rats model
- An inhibitory effect of tumor necrosis factor-alpha antagonist to gene expression in monocrotalineinduced pulmonary hypertensive rats model
- Kwon J.H.; Kim K.C.; Cho M.-S.; Kim H.S.; Sohn S.; Hong Y.M.
- Ewha Authors
- 홍영미; 김혜순; 손세정; 조민선; 김관창
- SCOPUS Author ID
- 홍영미; 김혜순; 손세정; 조민선; 김관창
- Issue Date
- Journal Title
- Korean Journal of Pediatrics
- Korean Journal of Pediatrics vol. 56, no. 3, pp. 116 - 124
- Document Type
- Purpose: Tumor necrosis factor (TNF)-α is thought to contribute to pulmonary hypertension. We aimed to investigate the effect of infliximab (TNF-α antagonist) treatment on pathologic findings and gene expression in a monocrotaline-induced pulmonary hypertension rat model. Methods: Six-week-old male Sprague-Dawley rats were allocated to 3 groups: control (C), single subcutaneous injection of normal saline (0.1 mL/kg); monocrotaline (M), single subcutaneous injection of monocrotaline (60 mg/kg); and monocrotaline + infliximab (M+I), single subcutaneous injection of monocrotaline plus single subcutaneous injection of infliximab (5 mg/kg). The rats were sacrificed after 1, 5, 7, 14, or 28 days. We examined changes in pathology and gene expression levels of TNF-α, endothelin-1 (E T-1), endothelin receptor A (ERA), endothelial nitric oxide synthase (eNOS), matrix metalloproteinase (MMP) 2, and tissue inhibitor of matrix metalloproteinase (TIMP). Results: The increase in medial wall thickness of the pulmonary arteriole in the M+I group was significantly lower than that in the M group on day 7 after infliximab treatment (P<0.05). The number of intraacinar muscular arteries in the M+I group was lower than that in the M group on days 14 and 28 (P< 0.05). Expression levels of TNF-α, ET-1, ERA, and MMP2 were significantly lower in the M+I group than in the M group on day 5, whereas eNOS and TIMP expressions were late in the M group (day 28). Conclusion: Infliximab administration induced early changes in pathological findings and expression levels of TNF-α, and MMP2 in a monocrotaline-induced pulmonary hypertension rat model. © 2013 by The Korean Pediatric Society.
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