PMID- 32655800
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20200928
IS  - 1943-8141 (Print)
IS  - 1943-8141 (Electronic)
IS  - 1943-8141 (Linking)
VI  - 12
IP  - 6
DP  - 2020
TI  - Ezetimibe protects against spinal cord injury by regulating autophagy and 
      apoptosis through inactivation of PI3K/AKT/mTOR signaling.
PG  - 2685-2694
AB  - Spinal cord injury (SCI) is a severe traumatic disease of the central nervous 
      system characterized by high incidence and disability rate. We aimed to 
      investigate the therapeutic potential of Ezetimibe (Eze) in SCI and identify the 
      underlying mechanisms. Acute SCI rat model was established by using the modified 
      weight-drop method. Following administration with Eze, the neurological function 
      was evaluated using the Basso, Beattie, and Bresnahan (BBB) locomotor scale 
      score, and the motor neurons were stained with Nissl staining. The pathological 
      changes of spinal cord tissues were tested using Hematoxylin and eosin staining. 
      The presence of apoptotic cells was examined using Terminal dexynucleotidyl 
      transferase-mediated dUTP nick end labeling (TUNEL) staining. Moreover, the 
      expression of main autophagy markers LC3II/I, Beclin1 and p62 and 
      apoptosis-related proteins was tested using western blot analysis. The changes of 
      PI3K/AKT/mTOR signaling-associated proteins were measured. Experimental results 
      showed that Eze treatment obviously improved functional recovery, the neuronal 
      survival and morphological characteristics of spinal cord. Additionally, Eze 
      administration dramatically upregulated the expression of LC3II/I and Beclin1 
      whereas downregulated that of p62. Concurrently, significantly reduced apoptosis 
      was observed following Eze intervention, accompanied by increased expression of 
      anti-apoptotic protein Bcl-2 and decreased expression of pro-apoptotic proteins 
      Bax, cleaved caspase-3 and cleaved caspase-9. Further results indicated that Eze 
      treatment remarkably suppressed the expression of phospho-PI3K (p-PI3K), p-AKT 
      and p-mTOR. These findings demonstrated that Eze could protect against SCI by 
      activating autophagy and hindering apoptosis through regulating PI3K/AKT/mTOR 
      signaling, suggesting a potential candidate for SCI therapy.
CI  - AJTR Copyright (c) 2020.
FAU - Chen, Gang
AU  - Chen G
AD  - Orthopedics Department, Union Hospital Affiliated to Fujian Medical University 
      Fuzhou 350000, Fujian Province, China.
FAU - Li, Jiandong
AU  - Li J
AD  - Orthopedics Department, Union Hospital Affiliated to Fujian Medical University 
      Fuzhou 350000, Fujian Province, China.
FAU - Wang, Zhenyu
AU  - Wang Z
AD  - Orthopedics Department, Union Hospital Affiliated to Fujian Medical University 
      Fuzhou 350000, Fujian Province, China.
FAU - Liu, Wenge
AU  - Liu W
AD  - Orthopedics Department, Union Hospital Affiliated to Fujian Medical University 
      Fuzhou 350000, Fujian Province, China.
LA  - eng
PT  - Journal Article
DEP - 20200615
PL  - United States
TA  - Am J Transl Res
JT  - American journal of translational research
JID - 101493030
PMC - PMC7344056
OTO - NOTNLM
OT  - Ezetimibe
OT  - PI3K
OT  - Spinal cord injury
OT  - apoptosis
OT  - autophagy
OT  - mTOR
COIS- None.
EDAT- 2020/07/14 06:00
MHDA- 2020/07/14 06:01
PMCR- 2020/06/15
CRDT- 2020/07/14 06:00
PHST- 2020/02/20 00:00 [received]
PHST- 2020/05/25 00:00 [accepted]
PHST- 2020/07/14 06:00 [entrez]
PHST- 2020/07/14 06:00 [pubmed]
PHST- 2020/07/14 06:01 [medline]
PHST- 2020/06/15 00:00 [pmc-release]
PST - epublish
SO  - Am J Transl Res. 2020 Jun 15;12(6):2685-2694. eCollection 2020.