Hepatic Cryoablation–Induced Multisystem Injury: Bioluminescent Detection of NF-κB Activation in a Transgenic Mouse Model

Autor:	Sadikot, Ruxanna T., Wudel Jr., L. James, Jansen, Duco E., Debelak, Jacob P., Yull, Fiona E., Christman, John W., Blackwell, Timothy S., Chapman, William C., Wudel, L James
Předmět:	LIVER injuries MULTIPLE organ failure TRANSCRIPTION factors LIVER surgery ANIMAL experimentation BIOLOGICAL models COMPARATIVE studies CRYOSURGERY ENZYME-linked immunosorbent assay KIDNEYS LIVER LUMINESCENCE spectroscopy LUNGS RESEARCH methodology MEDICAL cooperation MICE RESEARCH RISK assessment DNA-binding proteins EVALUATION research
Zdroj:	Journal of Gastrointestinal Surgery; Mar2002, Vol. 6 Issue 2, p264-270, 7p
Abstrakt:	Hepatic injury from cryoablation has been associated with multisystem injury, including adult respiratory distress syndrome, renal insufficiency, and coagulopathy; but the responsible mechanisms have not been well defined. In the present study we investigated the role of the transcription factor NF-κB in the multiorgan inflammatory response to hepatic cryoablation utilizing a novel in vivo system for determining NF-κB activity. Using transgenic mice expressing photinus luciferase under the control of the 5′ HIV-LTR (an NF-κB–dependent promoter), we measured luciferase activity in the liver, lungs, and kidneys as a marker for NF-κB activity. Luciferase production was determined by in vivo bioluminescence and by luciferase assays of tissue homogenates. After measurement of basal luciferase activity, mice were treated with 35% hepatic cryoablation or sham laparotomy and injected with luciferin (0.75 mg/mouse). Photon emission from the liver, lungs, and kidneys was measured at multiple time points. Hepatic cryoablation induced a significant increase in photon emission by the liver, lungs, and kidneys, which correlated with markedly increased luciferase activity measured from each organ after death. Lung lavage 4 hours after cryoablation showed neutrophilic lung inflammation with increased MIP-2 levels compared with sham surgery. These findings demonstrate that 35% hepatic cryoablation is associated with NF-κB activation in the remnant liver and multiple distant sites, and may be causally related to the multisystem injury that is seen after direct liver injury. ( J Gastrointest Surg 2002;6:264–270.) [Copyright &y& Elsevier]
Databáze:	Complementary Index
Externí odkaz:	Zobrazit plný text záznamu Full text from SpringerLink