Tetrahydropalmatine: Orchestrating survival – Regulating autophagy and apoptosis via the PI3K/AKT/mTOR pathway in perforator flaps

Xuankuai Chen; Kejian Fu; Yingying Lai; Chengji Dong; Zhuliu Chen; Yingying Huang; Guangyao Li; Renhao Jiang; Hongqiang Wu; Anyuan Wang; Shaojie Huang; Liyan Shen; Weiyang Gao; Shi Li

Biomedicine & Pharmacotherapy (Dec 2023)

Tetrahydropalmatine: Orchestrating survival – Regulating autophagy and apoptosis via the PI3K/AKT/mTOR pathway in perforator flaps

Xuankuai Chen,
Kejian Fu,
Yingying Lai,
Chengji Dong,
Zhuliu Chen,
Yingying Huang,
Guangyao Li,
Renhao Jiang,
Hongqiang Wu,
Anyuan Wang,
Shaojie Huang,
Liyan Shen,
Weiyang Gao,
Shi Li

Affiliations

Xuankuai Chen: Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou 325027, China; Key Laboratory of Orthopaedics of Zhejiang Province, Wenzhou 325027, China; The Second School of Medicine, Wenzhou Medical University, Wenzhou 325027, China
Kejian Fu: Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou 325027, China; Key Laboratory of Orthopaedics of Zhejiang Province, Wenzhou 325027, China; The Second School of Medicine, Wenzhou Medical University, Wenzhou 325027, China
Yingying Lai: Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou 325027, China; Key Laboratory of Orthopaedics of Zhejiang Province, Wenzhou 325027, China; The Second School of Medicine, Wenzhou Medical University, Wenzhou 325027, China
Chengji Dong: Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou 325027, China; Key Laboratory of Orthopaedics of Zhejiang Province, Wenzhou 325027, China; The Second School of Medicine, Wenzhou Medical University, Wenzhou 325027, China
Zhuliu Chen: Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou 325027, China; Key Laboratory of Orthopaedics of Zhejiang Province, Wenzhou 325027, China; The Second School of Medicine, Wenzhou Medical University, Wenzhou 325027, China
Yingying Huang: Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou 325027, China; Key Laboratory of Orthopaedics of Zhejiang Province, Wenzhou 325027, China; The Second School of Medicine, Wenzhou Medical University, Wenzhou 325027, China
Guangyao Li: Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou 325027, China; Key Laboratory of Orthopaedics of Zhejiang Province, Wenzhou 325027, China; The Second School of Medicine, Wenzhou Medical University, Wenzhou 325027, China
Renhao Jiang: Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou 325027, China; Key Laboratory of Orthopaedics of Zhejiang Province, Wenzhou 325027, China; The Second School of Medicine, Wenzhou Medical University, Wenzhou 325027, China
Hongqiang Wu: Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou 325027, China; Key Laboratory of Orthopaedics of Zhejiang Province, Wenzhou 325027, China; The Second School of Medicine, Wenzhou Medical University, Wenzhou 325027, China
Anyuan Wang: Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou 325027, China; Key Laboratory of Orthopaedics of Zhejiang Province, Wenzhou 325027, China; The Second School of Medicine, Wenzhou Medical University, Wenzhou 325027, China
Shaojie Huang: Wenzhou Medical University School of Laboratory Medicine and Life Sciences, China
Liyan Shen: Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou 325027, China; Key Laboratory of Orthopaedics of Zhejiang Province, Wenzhou 325027, China; The Second School of Medicine, Wenzhou Medical University, Wenzhou 325027, China
Weiyang Gao: Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou 325027, China; Key Laboratory of Orthopaedics of Zhejiang Province, Wenzhou 325027, China; The Second School of Medicine, Wenzhou Medical University, Wenzhou 325027, China
Shi Li: Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou 325027, China; Key Laboratory of Orthopaedics of Zhejiang Province, Wenzhou 325027, China; The Second School of Medicine, Wenzhou Medical University, Wenzhou 325027, China; Corresponding author at: Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou 325027, China.

Journal volume & issue: Vol. 169
p. 115887

Abstract

Read online

Background: Introduced in clinical practice in 1989, perforator flaps are vital for tissue defect repair, but they are challenged by distal necrosis. Tetrahydropalmatine (THP) from celandine is renowned for its anti-inflammatory and analgesic effects. This study investigates THP's use in perforator flaps. Methods: Thirty rats were divided into a control group and four THP concentration groups, while seventy-eight rats were categorized as control, THP, THP combined with rapamycin (RAP), and RAP alone. We created 11 cm by 2.5 cm multi-regional perforator flaps on rat backs, assessing survival blood flow and extracting skin flap tissue for autophagy, oxidative stress, apoptosis, and angiogenesis markers. Results: The THP group exhibited significantly reduced distal necrosis, increased blood flow density, and survival area on the seventh day compared to controls. Immunohistochemistry and Western blot results demonstrated improved anti-oxidative stress and angiogenesis markers, along with decreased autophagy and apoptosis indicators. Combining THP with RAP diminished flap survival compared to THP alone. This was supported by protein expression changes in the PI3K-AKT-mTOR pathway. Conclusion: THP enhances flap survival by modulating autophagy, reducing tissue edema, promoting angiogenesis, and mitigating apoptosis and oxidative stress. THP offers a potential strategy for enhancing multi-regional perforator flap survival through the PI3K/AKT/mTOR pathway. These findings highlight THP's promise in combatting perforator flap necrosis, uncovering a novel mechanism for its impact on flap survival.

Published in Biomedicine & Pharmacotherapy

ISSN: 0753-3322 (Print); 1950-6007 (Online)
Publisher: Elsevier
Country of publisher: France
LCC subjects: Medicine: Therapeutics. Pharmacology
Website: https://www.journals.elsevier.com/biomedicine-and-pharmacotherapy

About the journal

Abstract

Keywords