AUTHOR=Chen Zhengtai , Zhang Chenxi , Ma Haiwei , Huang Zihuai , Li Jiafeng , Lou Junshen , Li Baolong , Tu Qi , Gao Weiyang 

TITLE=Detrimental Effect of Sitagliptin Induced Autophagy on Multiterritory Perforator Flap Survival

JOURNAL=Frontiers in Pharmacology

VOLUME=Volume 11 - 2020

YEAR=2020

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2020.00951

DOI=10.3389/fphar.2020.00951

ISSN=1663-9812

ABSTRACT=Multiterritory perforator flap survival is commonly applied in surgical tissue reconstructions and covering of large skin defects. However, multiple risk factors such as ischemia, reperfusion injury and apoptosis after reconstructive surgeries cause necrosis in distal parts with outcomes ranging from poor aesthetic appearance to reconstructive failure. A few studies have reported that sitagliptin promotes angiogenesis and inhibits apoptosis. However, little is known about sitagliptin-induced autophagy especially on the flap model. Therefore, our study investigated the effect of sitagliptin and its induced autophagy on the perforator flap survival. Seventy-two male Sprague-Dawley rats were randomly separated into three groups; the first group of rats was treated with saline, the second group treated with sitagliptin and the third group treated with sitagliptin+3-methyladenine after developing a flap model. Results revealed that sitagliptin significantly promoted flap survival by enhancing angiogenesis, reducing oxidative stress, and attenuating apoptosis. In addition, flap survival was further improved after co-administration with 3-methyladenine to inhibit autophagy. Overall, our results established that sitagliptin has positive effects in promoting survival of multiterritory perforator flap. Sitagliptin-induced autophagy was detrimental for flap survival and its inhibition may further improve flap survival.