Clinical and Experimental Pediatrics

대한소아청소년과학회 (The Korean Pediatric Society)
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An inhibitory effect of tumor necrosis factor-alpha antagonist to gene expression in monocrotaline-induced pulmonary hypertensive rats model

  • Kwon, Jung Hyun (Department of Pediatrics, Ewha Womans University School of Medicine) ;
  • Kim, Kwan Chang (Department of Thoracic and Cardiovascular Surgery, Ewha Womans University School of Medicine) ;
  • Cho, Min-Sun (Department of Pathology, Ewha Womans University School of Medicine) ;
  • Kim, Hae Soon (Department of Pediatrics, Ewha Womans University School of Medicine) ;
  • Sohn, Sejung (Department of Pediatrics, Ewha Womans University School of Medicine) ;
  • Hong, Young Mi (Department of Pediatrics, Ewha Womans University School of Medicine)
  • 투고 : 2012.07.31
  • 심사 : 2013.01.25
  • 발행 : 2013.03.15
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초록

Purpose: Tumor necrosis factor (TNF)-${\alpha}$ is thought to contribute to pulmonary hypertension. We aimed to investigate the effect of infliximab (TNF-${\alpha}$ 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-${\alpha}$, 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-${\alpha}$, 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-${\alpha}$, and MMP2 in a monocrotaline-induced pulmonary hypertension rat model.

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참고문헌

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