The protective effects of tumor necrosis factor receptor 1 deletion on hindlimb ischemia

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LI Changling()
WEI Ling()
WANG Jian'an()
Journal Title:
Volume 15, Issue 03, 2006
Key Word:
Tumor necrosis factor α receptor 1;Hindlimb ischemia;Apoptosis

Abstract: Objective Signals in the tumor necrosis factor α TNFα pathway, including TNFα and tumor necrosis factor α receptor 1TNFR1, are upregulated after acute hindlimh ischemia. It is unclear, however, whether this upregulation is apathophysiological consequence or a compensatory response. In the present study, the effect of TNFR1 deletion in a mouse model of hindlimb ischemia was investigated.Methods Hindlimb ischemia was produced through ligation of the proximal and distal left femoral artery and its branches in TNFR1 knockout TNFR1-/- and wild type WT mice. Laser Doppler blood flow measurement showed that limb perfusion was significantly higher in TNFR1-/- mice than that in the WT mice at 1 day after operation.Results The calculated ischemic scores were 3.67 ± 0.52 in WT group and 1.83 ± 0.41 in TNFR1-/- group P <0.05. The rate of amputation was 50% in WT mice versus 0% in TNFR1-/- mice. There were less TUNEL positive cells in the calf muscle of TNFR1-/- mice than that of WT mice. Furthermore, DNA fragmentation was more obvious in WT mice.Western blot showed less expression of Bax and cleaved caspase 3 in TNFR1-/- mice 1 day after ischemia, suggesting a reduced apoptotic process in the absence of TNFR1.Conclusion In mice with hindlimb ischemia, knockout of TNFR1 prevents the activation of death-related proteins down streaming to TNF α and attenuated cell death including apoptosis. Systemic block of the TNFR1 might be a new interventional methods-to preserve the limbs from acute ischemic attack in patients with peripheral arterial obstructive disease.

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