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Ischemic preconditioning ameliorates microcirculatory disturbance through downregulation of TNF-alpha production in a rat cremaster muscle model

  • Original Paper
  • Published:
Journal of Biomedical Science

Abstract

Ischemia-reperfusion (I/R) injury is a complex process involving the generation and release of inflammatory cytokines, and the accumulation and infiltration of neutrophils and macrophages, which disturbs the microcirculatory hemodynamics. Nonetheless, ischemic preconditioning (IPC) is known to produce immediate tolerance to subsequent prolonged I/R insults, although its underlying mechanism largely remains unknown. Our study investigated the role of the IκB-α-NF-κB-TNF-α (tumor necrosis factor-α) pathway in IPC's ability to ameliorate I/R-induced microcirculatory disturbances in rat cremaster muscle flaps. Male Sprague-Dawley rats were randomized (n=8 per group) into 3 groups: a sham-operated control group, an I/R group (4 h of pudic epigastric artery ischemia followed by 2 h of reperfusion), and an IPC+I/R group (3 cycles of 10 min of ischemia followed by 10 min reperfusion before I/R). Intravital microscopy was used to observe leukocyte/endothelial cell interactions and quantify functional capillaries in cremaster muscles. I/R markedly increased the number of rolling, adhering, and migrating leukocytes. It was also observed that I/R significantly increased TNF-α expression in these injured tissues. On the other hand, IPC prevented I/R-induced increases in leukocyte rolling, adhesion, and transmigration. Moreover, TNF-α protein production and its mRNA expression were downregulated in the IPC group. Finally, I/R-induced IκB-α phosphorylation and NF-κB (p65) nuclear translocation were both suppressed by IPC. These results indicated that IPC attenuated NF-κB activation and subsequently reduced TNF-α expression, which resulted in the amelioration of microcirculatory disturbances in I/R-injured cremaster muscles.

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Authors and Affiliations

  1. Department of Life Science, Chang Gung University, Chang Gung Memorial Hospital, Taoyuan, Taiwan

    Li-Man Hung, Yi-Jen Hsueh & Wing-Keung Chu

  2. Plastic and Reconstructive Surgery, College of Medicine, Chang Gung University, Chang Gung Memorial Hospital, Taoyuan, Taiwan

    William Wei & Fu-Chan Wei MD

  3. Microcirculatory Laboratory, Department of Plastic and Reconstructive Surgery, Chang Gung Memorial Hospital, No. 5 Fu-Shin Street, 333, Kweishan, Taoyuan, Taiwan

    Fu-Chan Wei MD

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Hung, LM., Wei, W., Hsueh, YJ. et al. Ischemic preconditioning ameliorates microcirculatory disturbance through downregulation of TNF-alpha production in a rat cremaster muscle model. J Biomed Sci 11, 773–780 (2004). https://doi.org/10.1007/BF02254362

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  • DOI: https://doi.org/10.1007/BF02254362

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