Detrimental Effect of Sitagliptin Induced Autophagy on Multiterritory Perforator Flap Survival

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

doi:10.3389/fphar.2020.00951

Detrimental Effect of Sitagliptin Induced Autophagy on Multiterritory Perforator Flap Survival

Front Pharmacol. 2020 Jun 26:11:951. doi: 10.3389/fphar.2020.00951. eCollection 2020.

Authors

Zhengtai Chen^{1

2

3}, Chenxi Zhang^{1

2

3}, Haiwei Ma^{1

2

3}, Zihuai Huang^{1

2

3}, Jiafeng Li^{1

2

3}, Junshen Lou^{1

2

3}, Baolong Li^{1

2

3}, Qi Tu^{4

5}, Weiyang Gao^{1

2}

Affiliations

¹ Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China.
² Department of Orthopaedics, Zhejiang Provincial Key Laboratory of Orthpaedics, Wenzhou, China.
³ Department of Second Clinical Medical, The Second Clinical Medical College of Wenzhou Medical University, Wenzhou, China.
⁴ Department of Neurosurgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
⁵ Department of First Clinical Medical, The First Clinical Medical College of Wenzhou Medical University, Wenzhou, China.

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 (Sit) promotes angiogenesis and inhibits apoptosis. However, little is known about Sit-induced autophagy especially on the flap model. Therefore, our study investigated the effect of Sit and its induced autophagy on the perforator flap survival. Ninety male Sprague-Dawley rats were randomly separated into control, Sit, and Sit+3-methyladenine group. Results revealed that Sit 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 Sit has positive effects in promoting survival of multiterritory perforator flap. Sit-induced autophagy was detrimental for flap survival and its inhibition may further improve flap survival.

Keywords: PI3K/Akt signaling pathway; angiogenesis; apoptosis; autophagy; multiterritory perforator flap; oxidative stress; sitagliptin.