Zhongjie Zhang*, Yan Xu, Songyuan Chi and Longji Cui Pages 140 - 146 ( 7 )
Background: Propofol is an intravenous drug commonly used in anesthesia procedures and intensive care in children. However, it also has neurotoxic effects on children. MicroRNA plays an important role in neurological diseases and neurotoxicity.
Methods: In this study, primary rat hippocampal neurons were used to investigate the role of miR- 582-5p in propofol-induced neurotoxicity. Cell viability was monitored by 3-(4,5-dimethylthiazolyl)- 2,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, while the expression of proteins was monitored by real-time quantitation polymerase chain reaction (RT-qPCR) and western blot. TargetScan and double luciferase report assay were used to predict the targeting relationship between miR-582-5p and Rho-associated serine-threonine protein kinase 1 (ROCK1).
Results: In the present study, the viability of neurons and the expression of miR-582-5p were decreased in a time-dependent manner after propofol treatment. Besides, miR-582-5p overexpression significantly reduced the toxicity of propofol on neuron cells but had no significant effect on normal nerve cells. In addition, miR-582-5p overexpression significantly reversed the expression of apoptosis-related proteins (cleaved caspase 3 and cleaved caspase 9) induced by propofol but had no significant effect in normal nerve cells. TargetScan and Dual-luciferase report assay revealed that ROCK1 was a targeted regulatory gene for miR-582-5p, and propofol treatment up-regulated ROCK1 expression by inhibiting miR-582-5p expression. Notably, miR-582-5p overexpression significantly increased cell viability, while ROCK1 overexpression reversed the effect of miR-582- 5p.
Conclusion: Taken together, these findings suggest that miR-582-5p alleviated propofol-induced apoptosis of newborn rat neurons by inhibiting ROCK1.
MicroRNA-582-5p, propofol, neurotoxicity, Rho-associated serine-threonine protein kinase1 (ROCK)1, apoptosis.
Department of Anesthesiology, The Affiliated Hospital of Beihua University, Jilin City, Jilin Province, 132000, Department of Endocrinology, The Affiliated Hospital of Beihua University, Jilin City, Jilin Province, 132000, Department of Anesthesiology, The Affiliated Hospital of Beihua University, Jilin City, Jilin Province, 132000, Department of Anesthesiology, The Affiliated Hospital of Beihua University, Jilin City, Jilin Province, 132000