Korean J Pediatr.  2013 Mar;56(3):116-124. 10.3345/kjp.2013.56.3.116.

An inhibitory effect of tumor necrosis factor-alpha antagonist to gene expression in monocrotaline-induced pulmonary hypertensive rats model

• Kwon JH
• Kim KC
• Cho MS
• Kim HS
• Sohn S
• Hong YM

• KMID: 2284282
• DOI: http://doi.org/10.3345/kjp.2013.56.3.116

Abstract

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 intra-acinar 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.

Keyword

Pulmonary hypertension; Monocrotaline; Gene expression; Infliximab

MeSH Terms

Animals
Antibodies, Monoclonal
Arteries
Arterioles
Endothelin-1
Gene Expression
Humans
Hypertension, Pulmonary
Injections, Subcutaneous
Male
Monocrotaline
Nitric Oxide Synthase Type III
Rats
Rats, Sprague-Dawley
Receptors, Endothelin
Tumor Necrosis Factor-alpha
Infliximab
Antibodies, Monoclonal
Endothelin-1
Monocrotaline
Nitric Oxide Synthase Type III
Receptors, Endothelin
Tumor Necrosis Factor-alpha