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

Background: Thioredoxin-1 (Trx-1) plays an important role in defensing the skin flap ischemia-reperfusion injury. Ganoderma lucidum polysaccharide peptide (GLPP) is the major component of Ganoderma lucidum, which possesses potent antioxidant and antiapoptotic activity. Our study aims to determine whether GLPP could attenuate the skin flap ischemia-reperfusion injury and investigate possible mechanisms involved. Methods: The dermoprotective effect and mechanisms were assessed by an in vivo mouse ischemia-reperfusion flap model and an in vitro epithelial skin cell hypoxia/reoxygenation model. GLPP was administered to mice and cells before the procedures of ischemia-reperfusion and hypoxia/reoxygenation, respectively. Trx-1 inhibitor PX-12 was introduced in the counterevidence group. The flap tissues and cells were tested by hematoxylin-eosin and immunohistochemistry staining, TUNEL assay, SOD and MDA measurement, and Western blot. Results: The survival rates of ischemia-reperfusion flaps and hypoxia/reoxygenation cells increased significantly following GLPP treatment. Mitigated tissue damage, reduced apoptosis, and enhanced antioxidant activity were observed in ischemia-reperfusion flaps replenishing GLPP. Western blot analysis revealed Trx-1 depletion and a remarkable increase in ASK-1, p-p38, cl-caspase-3 and c-PARP abundance in ischemia-reperfusion flaps and hypoxia/reoxygenation cells, while GLPP dramatically upregulated Trx-1 and reduced the apoptosis-related protein expression. However, the rescue effect of GLPP was notably blunted by supplementation with PX-12. Conclusions: Our investigation highlights the protective role of GLPP in skin flap ischemia-reperfusion injury through Trx-1-dependent antioxidant and antiapoptotic pathway. This initial foray demonstrates the therapeutic value of GLPP against ischemia-reperfusion and facilitates the understanding of its dermoprotective mechanism. Disclosure: The authors have no financial interest to disclose in relation to the content of this article. Acknowledgements: The authors thank Prof. Baoxue Yang, Peking University Health Science Center, and Prof. Zhibin Lin, Fuzhou Institute of Green Valley Bio-Pharm Technology, for kindly providing the compound of Ganoderma lucidum polysaccharide peptide. This work was supported by National Natural Science Foundation of China (grants No. 81703167, 81703591). *Corresponding author: Address correspondence to: Zhuming Yin, M.D., Department of Breast Reconstruction, Tianjin Medical University Cancer Institute and Hospital, Tiyuanbei, Huanhu West Road, Hexi District, Tianjin 300060, China. Phone: +86-22-23340123-1173, E-mail: yinzhuming@tmu.edu.cn ©2018American Society of Plastic Surgeons