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

Abstract

Objective: To observe the inhibitory effects of the peroxisome proliferator-activated receptor alpha (PPARa) 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-kB), 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 PPARa 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 PPARa 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: PPARa 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.