期刊
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY
卷 284, 期 3, 页码 H804-H814出版社
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpheart.00394.2001
关键词
N-acetyl-leucinyl-leucinyl-norleucinal; collagenase digestion; cardiac contractile function; fura 2-AM
资金
- NIGMS NIH HHS [2-P50-GM-21681-36] Funding Source: Medline
This study examined the effects of either IkappaBalpha overexpression (transgenic mice) or N-acetyl-leucinyl-leucinyl- norleucinal (ALLN) administration (proteosome inhibitor in wild-type mice) on cardiomyocyte secretion of tumor necrosis factor-alpha (TNF-alpha) and on cardiac performance after burn trauma. Transgenic mice were divided into four experimental groups. IkappaBalpha overexpressing mice were given a third-degree scald burn over 40% of the total body surface area or wild-type littermates were given either a scald or sham burn to provide appropriate controls. Pharmacological studies included ALLN (20 mg/kg) administration in either burned wild-type mice or wild-type shams. Burn trauma in wild-type mice promoted nuclear factor-kappaB (NF-kappaB) nuclear translocation, cardiomyocyte secretion of TNF-alpha, and impaired cardiac performance. IkappaBalpha overexpression or ALLN treatment of burn trauma prevented NF-kappaB activation in cardiac tissue, prevented cardiomyocyte secretion of TNF-alpha, and ablated burn-mediated cardiac contractile dysfunction. These data suggest that NF-kappaB activation and inflammatory cytokine secretion play a significant role in postburn myocardial abnormalities.
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