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KMID : 1130320130560030116
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Korean Journal of Pediatrics
2013 Volume.56 No. 3 p.116 ~ p.124
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An inhibitory effect of tumor necrosis factor-alpha antagonist to gene expression in monocrotalineinduced pulmonary hypertensive rats model
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Kwon Jung-Hyun
Kim Hae-Soon
Sohn Se-Jung
Hong Young-Mi
Kim Kwan-Chang
Cho Min-Sun
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Abstract
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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 (ET-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.
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KEYWORD
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Pulmonary hypertension, Monocrotaline, Gene expression, Infliximab
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