Aging
Navigate
Submit an Article
Research Paper|Volume 13, Issue 22|pp 24640—24654

PPARα agonist relieves spinal cord injury in rats by activating Nrf2/HO-1 via the Raf-1/MEK/ERK pathway

Haocong Zhang1, Dulei Xiang1,2, Xinwei Liu1, Liangbi Xiang1
  • 1The Department of Orthopedics, General Hospital of Northern Theater Command of Chinese People’s Liberation Army, Shenyang, Liaoning, China
  • 2Jinzhou Medical University Graduate Training Base of General Hospital of Northern Theater Command, Jinzhou, Liaoning, China
* Equal contribution
Received: April 3, 2021Accepted: October 25, 2021Published: November 19, 2021
https://doi.org/10.18632/aging.203699

Copyright: © 2021 Zhang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Objective: To observe the inhibitory effects of the peroxisome proliferator-activated receptor alpha (PPARα) agonist palmitoylethanolamide (PEA) on inflammatory responses and oxidative stress injury in rats with spinal cord injury (SCI).

Methods: The SCI rat model was established using modified Allen's method and the changes in rats’ joint motion were observed by Basso, Beattie and Bresnahan locomotor rating scale (BBB scale) at 1, 3 and 7 days after modeling, HE Staining and Nissl Staining has been carried out to evaluate the pathological lesion of spinal cords in rats. Besides, Immunohistochemical (IHC) was performed to detect the reactive oxygen species (ROS), expression levels of acrylamide (ACR) and manganese superoxide dismutase (MnSOD) in rat spinal cords, and Western Blotting was applied to measure protein expression levels of nuclear factor-kappa B (NF-κB), B cell lymphoma-2 (Bcl-2), BCL-2 associated X (BAX), phosphoinositide 3-kinase (PI3K), protein kinase B (Akt), phosphorylated (p)-Akt, HO-1, Nrf2, trithorax-1 (TRX-1), Raf-1, MEK, ERK, p-MEK and p-ERK.

Results: The PPARα agonist PEA could alleviate SCI in rats, inhibit inflammatory responses, mitigate oxidative stress injury, reduce the apoptotic rate and promote SCI rats motor function recovery. In addition, the PPARα agonist PEA was able to activate the phosphorylation of MEK and ERK, stimulate Nrf-2 translocation into the nucleus and up-regulate the expressions of HO-1 and TRX-1.

Conclusion: PPARα agonist PEA can relieve SCI in rats by inhibiting inflammatory responses and oxidative stress, which may involve a mechanism associated with the activation of Nrf2/HO-1 via the Raf-1/MEK/ERK pathway.