Frontiers in Pharmacology (Sep 2019)
Betulinic Acid Enhances the Viability of Random-Pattern Skin Flaps by Activating Autophagy
- Jiafeng Li,
- Jiafeng Li,
- Jiafeng Li,
- Guodong Bao,
- Guodong Bao,
- Guodong Bao,
- Eman ALyafeai,
- Jian Ding,
- Jian Ding,
- Jian Ding,
- Shihen Li,
- Shihen Li,
- Shihen Li,
- Shimin Sheng,
- Zitong Shen,
- Zhenyu Jia,
- Chen Lin,
- Chen Lin,
- Chen Lin,
- Chenxi Zhang,
- Chenxi Zhang,
- Chenxi Zhang,
- Zhiling Lou,
- Zhiling Lou,
- Zhiling Lou,
- Huazi Xu,
- Huazi Xu,
- Huazi Xu,
- Weiyang Gao,
- Weiyang Gao,
- Weiyang Gao,
- Kailiang Zhou,
- Kailiang Zhou,
- Kailiang Zhou
Affiliations
- Jiafeng Li
- Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, China
- Jiafeng Li
- Zhejiang Provincial Key Laboratory of Orthopaedics, Wenzhou, China
- Jiafeng Li
- The Second Clinical Medical College of Wenzhou Medical University, Wenzhou, China
- Guodong Bao
- Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, China
- Guodong Bao
- Zhejiang Provincial Key Laboratory of Orthopaedics, Wenzhou, China
- Guodong Bao
- The Second Clinical Medical College of Wenzhou Medical University, Wenzhou, China
- Eman ALyafeai
- School of Pharmaceutical Science, Wenzhou Medical University, Wenzhou, China
- Jian Ding
- Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, China
- Jian Ding
- Zhejiang Provincial Key Laboratory of Orthopaedics, Wenzhou, China
- Jian Ding
- The Second Clinical Medical College of Wenzhou Medical University, Wenzhou, China
- Shihen Li
- Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, China
- Shihen Li
- Zhejiang Provincial Key Laboratory of Orthopaedics, Wenzhou, China
- Shihen Li
- The Second Clinical Medical College of Wenzhou Medical University, Wenzhou, China
- Shimin Sheng
- The Second Clinical Medical College of Wenzhou Medical University, Wenzhou, China
- Zitong Shen
- Renji College of Wenzhou Medical University, Wenzhou, China
- Zhenyu Jia
- School of Pharmaceutical Science, Wenzhou Medical University, Wenzhou, China
- Chen Lin
- Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, China
- Chen Lin
- Zhejiang Provincial Key Laboratory of Orthopaedics, Wenzhou, China
- Chen Lin
- The Second Clinical Medical College of Wenzhou Medical University, Wenzhou, China
- Chenxi Zhang
- Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, China
- Chenxi Zhang
- Zhejiang Provincial Key Laboratory of Orthopaedics, Wenzhou, China
- Chenxi Zhang
- The Second Clinical Medical College of Wenzhou Medical University, Wenzhou, China
- Zhiling Lou
- Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, China
- Zhiling Lou
- Zhejiang Provincial Key Laboratory of Orthopaedics, Wenzhou, China
- Zhiling Lou
- The Second Clinical Medical College of Wenzhou Medical University, Wenzhou, China
- Huazi Xu
- Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, China
- Huazi Xu
- Zhejiang Provincial Key Laboratory of Orthopaedics, Wenzhou, China
- Huazi Xu
- The Second Clinical Medical College of Wenzhou Medical University, Wenzhou, China
- Weiyang Gao
- Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, China
- Weiyang Gao
- Zhejiang Provincial Key Laboratory of Orthopaedics, Wenzhou, China
- Weiyang Gao
- The Second Clinical Medical College of Wenzhou Medical University, Wenzhou, China
- Kailiang Zhou
- Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, China
- Kailiang Zhou
- Zhejiang Provincial Key Laboratory of Orthopaedics, Wenzhou, China
- Kailiang Zhou
- The Second Clinical Medical College of Wenzhou Medical University, Wenzhou, China
- DOI
- https://doi.org/10.3389/fphar.2019.01017
- Journal volume & issue
-
Vol. 10
Abstract
Random-pattern skin flap replantation is commonly used to repair skin defects during plastic and reconstructive surgery. However, flap necrosis due to ischemia and ischemia–reperfusion injury limits clinical applications. Betulinic acid, a plant-derived pentacyclic triterpene, may facilitate flap survival. In the present study, the effects of betulinic acid on flap survival and the underlying mechanisms were assessed. Fifty-four mice with a dorsal random flap model were randomly divided into the control, betulinic acid group, and the betulinic acid + 3-methyladenine group. These groups were treated with dimethyl sulfoxide, betulinic acid, and betulinic acid plus 3-methyladenine, respectively. Flap tissues were acquired on postoperative day 7 to assess angiogenesis, apoptosis, oxidative stress, and autophagy. Betulinic acid promoted survival of the skin flap area, reduced tissue edema, and enhanced the number of microvessels. It also enhanced angiogenesis, attenuated apoptosis, alleviated oxidative stress, and activated autophagy. However, its effects on flap viability and angiogenesis, apoptosis, and oxidative stress were reversed by the autophagy inhibitor 3-methyladenine. Our findings reveal that betulinic acid improves survival of random-pattern skin flaps by promoting angiogenesis, dampening apoptosis, and alleviating oxidative stress, which mediates activation of autophagy.
Keywords
