Micro surgeon faces broad array of complicated procedures in its daily practice, from well-planned elective free tissue transfer to unexpected emergency traumatic limb amputation. Most of these events apparently have something in common, an inevitable ischemic period. Sometimes it would be prolonged and exceed tissue toleration time, such as late amputate delivery or a consequent secondary ischemia due to spasm or thrombosis. After reestablishment of blood supply, these instances would potentially trigger ischemia-reperfusion injury.1 A cascade of catastrophic events consist of ROS (Reactive Oxygen Species) overproduction, inflammatory response, depleted NO (nitric oxide), capillary thrombosis, mitochondrial dysfunction, and apoptosis that lead to tissue damage increment despite of newly oxygen supply.2-3
Mechanical, pharmacological, and genetic engineering strategies were made as an effort to attenuate ischemia-reperfusion injury harms, they were as simple as remote extremity transient preconditioning ischemia, or medication like lidocaine, until sophisticated method using gene transfer using human adenovirus.4-6 Basicly they worked through manipulation of its current recognized molecular events such as mentioned above.7
Telomerase-based 16-mer peptide vaccine represents amino acids sequence from human telomerase reverse transcriptase (hTERT), a subunit of telomerase enzyme that prevent chromosome end shortening and overexpressed in majority of malignant cells.8 Albeit of its anti-cancer potential through initiation of CD4 and CD8 T-cell responses by binds to human leucocyte antigen (HLA) class II, telomerase-based 16-mer peptide vaccine is also reported to possess anti-inflammatory, anti-apoptotic, and anti-oxidant properties through mimicking hTERT extra-telomeric function in rat neural stem cells.9 However, the role of this peptide vaccine in skin reperfusion injury has not yet been documented. Purpose of this study was to investigate the protective effect of telomerase-based 16-mer peptide vaccine in ischemia-reperfusion injury. Using rat superficial inferior epigastric island skin flap model, we evaluated flap viability, neutrophils tissue infiltration, malondialdehyde, SOD (superoxide dismutase) activity, IL-1, IL-6, and TNF-alpha.
Material and method
All animal procedures were approved by the Animal Research Committee of Seoul National University Bundang Hospital. Animals were individually maintained in animal laboratory center under a 12:12 light/dark cycle with ad libitum access to food and water. Thirty-six male Sprague-Dawley rats weighing 180 to 230 g were used in this experiment. Rats were separated into the following three groups:
Group I: sham group (flap only without ischemia) (n=13).
Group II: saline group (saline injection and 7 hours of ischemia) (n=13).
Group III: peptide vaccine group (telomerase-based 16-mer peptide vaccine injection and 7 hours of ischemia) (n=13).
From each group, 5 rats were...