Catalpol improves axonal outgrowth and reinnervation of injured sciatic nerve by activating Akt/mTOR pathway and regulating BDNF and PTEN expression

American Journal of Translational Research

Guoran Wan¹  Huifeng Zhu²  Yan Qiu³  Xian Yang⁴  Yuan Wang⁵ 

[1] Class 7 Grade 1, Chongqing Three Gorges Medical College, Chongqing 400016, China;College of Pharmaceutical Sciences and Traditional Chinese Medicine, Southwest University, Chongqing 400715, China;Department of Emergency and Critical Care Medicine, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China;Department of Pharmacy, The Seventh Peoples Hospital of Chengdu, Chengdu 610041, China;Engineering Research Center for Chongqing Pharmaceutical Process and Quality Control, Chongqing 400715, China

关键词: Catalpol;    sciatic nerve crush injury;    Akt/mTOR pathway;    axon regeneration;   

DOI  :  

学科分类：医学（综合）

来源: e-Century Publishing Corporation

【 摘 要 】

Aim: This study aimed to investigate the effects of catalpol on sciatic nerve crush injury (SNCI) and further explore the role of Akt/mTOR pathway in its pharmacological efficacy. Methods: Mice with SNCI in the right were treated with catalpol. Rapamycin was used to block mTOR signal activation. After sciatic motor nerve function was observed, the gastrocnemius muscles, injury sciatic nerve and spinal cord L4-L6 were isolated. TUNEL staining was done to assess the neuronal apoptosis; Transmission electron microscopy (TEM) was performed to observe the microstructure of regenerated myelinated nerve fibers. The expression of proteins in Akt/mTOR pathway, those related to axon regeneration and cell apoptosis was detected by Western blotting. Brain derived neurotrophic factor (BDNF), phosphatase and tensin homolog deleted on chromosome ten (PTEN), growth associated protein-43 (GAP-43), pro- and anti-apoptosis protein including Bax and BCL-2. Results: Catalpol significantly improved the function of injured sciatic motor nerve and facilitated the sciatic motor and sensory nerve fiber growth and the reinnervation of gastrocnemius muscles. TEM showed catalpol increased the density and thickness of regenerated myelinated nerve fibers, which exhibited a regular arrangement. Catalpol significantly reduced the number of apoptotic cells and increased the Bcl-2/Bax ratio in the L4-L6 spinal cord anterior horn. Importantly, catalpol significantly increased the expression of p-Akt, p-mTOR, p-p70S6K, GAP-43 and BDNF, but decreased PTEN expression. Blockade of mTOR activation was partially abrogated by catalpol. Conclusion: Catalpol may improve SCNI by enhancing the axonal growth via activating the Akt/mTOR pathway and modulating BDNF and PTEN expression.

【 授权许可】

CC BY-NC