Inhibition of SPRY2 expression protects sevoflurane-induced nerve injury via ERK signaling pathway

Abstract

Purpose: To investigate the effect of Sprouty2 (SPRY2) on sevoflurane (SEV) induced nerve injury in rats and its potential signaling pathway. Methods: Male Sprague-Dawley rats were divided into sham and SEV groups containing six rats per group. Neurological injury assessment and H & E staining were performed to evaluate the degree of nerve injury in the rats, while quantitative polymerase chain reaction (qPCR) and immunoblot assays were performed to confirm the expression levels of SPRY2 in hippocampus tissues. Morris water maze tests were performed to determine the degree of cognitive deficit in rats. TUNEL and immunoblot assays were performed to evaluate the effects of SPRY2 on the apoptosis of hippocampus tissues. Results: The SPRY2 expression was elevated in sevoflurane-induced hippocampus injury (p < 0.001). Ablation of SPRY2 inhibited sevoflurane-induced hippocampal neuron apoptosis (p < 0.001). In addition, depletion of SPRY2 promoted hippocampal neuron activity and decreased apoptosis (p < 0.001). Knockdown of SPRY2 promoted ERK signaling pathway, thereby protecting against sevoflurane-induced nerve injury and cognitive deficit in the rats (p < 0.001). Conclusion: Sevoflurane induces cognitive dysfunction and upregulates SPRY2 expression in brain tissues in rats. The SPRY2 knockdown improves SEV-induced neural injuries and cognitive deficits, inhibits hippocampal neuron apoptosis, and enhances its activity. Meanwhile, SPRY2 depletion protects SEV-induced nerve injury via the ERK pathway. Thus, Sprouty2 could serve as a promising drug target for the treatment of SEV-induced cognitive dysfunctions.