Ganoderma lucidum Polysaccharide Peptide Attenuates Skin Flap Ischemia-Reperfusion Injury in a Thioredoxin-Dependent Manner.

Thioredoxin-1 plays an important role in protecting the skin flap from ischemia-reperfusion injury. Ganoderma lucidum polysaccharide peptide is the major component of G. lucidum, which possesses potent antioxidant and antiapoptotic activity. This study aims to determine whether G. lucidum polysaccharide peptide could attenuate skin flap ischemia-reperfusion injury and to investigate possible mechanisms involved. G. lucidum polysaccharide peptide was administered to mice and epidermal cells before ischemia-reperfusion and hypoxia/reoxygenation, respectively. The thioredoxin-1 inhibitor PX-12 was introduced in the counterevidence group. The flap tissues and cells were tested by hematoxylin and eosin and immunohistochemistry staining, terminal deoxynucleotidyl transferase-mediated dUDP end-labeling assay, superoxide dismutase and malonic dialdehyde measurement, and Western blot. The survival rates of ischemia-reperfusion flaps and hypoxia/reoxygenation cells increased significantly following G. lucidum polysaccharide peptide treatment. Mitigated tissue damage, reduced apoptosis, and enhanced antioxidant activity were observed in ischemia-reperfusion flaps replenishing G. lucidum polysaccharide peptide. Western blot analysis revealed thioredoxin-1 depletion and a remarkable increase in ASK-1, phospho-p38, cleaved caspase-3, and cleaved PARP abundance in ischemia-reperfusion flaps and hypoxia/reoxygenation cells, whereas G. lucidum polysaccharide peptide dramatically up-regulated thioredoxin-1 and reduced the apoptosis-related protein expression. However, the rescue effect of G. lucidum polysaccharide peptide was notably blunted by supplementation with PX-12. The current investigation highlights the protective role of G. lucidum polysaccharide peptide in skin flap ischemia-reperfusion injury through a thioredoxin-1-dependent antioxidant and antiapoptotic pathway. This initial foray demonstrates the therapeutic value of G. lucidum polysaccharide peptide against ischemia-reperfusion and facilitates the understanding of its dermoprotective mechanism.