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Ezetimibe protects against spinal cord injury by regulating autophagy and apoptosis through inactivation of PI3K/AKT/mTOR signaling.

Abstract：

: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.

journal_name

Am J Transl Res

journal_title

American journal of translational research

authors

Chen G,Li J,Wang Z,Liu W

subject

Has Abstract

pub_date

2020-06-15 00:00:00

pages

2685-2694

issue

6

issn

1943-8141

journal_volume

12

pub_type

杂志文章

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