Effect of propofol on NR2B/CaMKIIα signaling pathway in brain injury induced by hepatic ischemia-reperfusion in preadolescent mice

Abstract

Objective To evaluate the effect of propofol on subunit 2B-containing N-methyl-D-aspartate receptor(NR2B)/calcium/calmodulin-dependent protein kinaseⅡ alpha (CaMKIIα) signaling pathway in brain injury induced by hepatic ischemia-reperfusion (I/R) in preadolescent mice. Methods Sixty-four healthy clean-grade C57BL/6 mice, aged 2 weeks, weighing 4-6 g, were randomized into 4 groups (n=16 each) using a random number table method: sham operation group (S group), hepatic I/R group (HI/R group), propofol control group (P group), and propofol plus hepatic I/R group (P+ HI/R group). The model of 70% liver I/R injury was established by clamping the left and middle lobe vascular trunk in anesthetized mice.Propofol 20 mg/kg was intraperitoneally injected before operation at 30 min before establishing the model in P and P+ HI/R groups.The equal volume of normal saline was given instead in P and P+ HI/R groups.Eight mice of each group were sacrificed at 6 h of reperfusion, hippocampal tissues were obtained for examination of pathological changes of hippocampal tissues and for determination of neuronal apoptosis (by TUNEL) and expression of NR2B, phosphorylated NR2B (p-NR2B), CaMKⅡα and phosphorylated CaMKⅡα (p-CaMKⅡα) (by Western blot). The remaining 8 mice in each group were used for Morris water maze test at 1 month after establishing the model.Apoptosis index was calculated. Results Compared with group S, the escape latency was significantly prolonged, the percentage of the time of staying at the original platform quadrant was decreased, the expression of p-NR2B and p-CaMKIIα was up-regulated, and apoptosis index was increased in HI/R and P+ HI/R groups (P 0.05). Compared with group HI/R, the escape latency was significantly shortened, the percentage of the time of staying at the original platform quadrant was increased, the expression of p-NR2B and p-CaMKIIα was down-regulated, and apoptosis index was decreased (P<0.05), and the pathological changes of hippocampal tissues were significantly attenuated in group P+ HI/R. Conclusion The mechanism by which propofol reduces brain injury induced by hepatic I/R may be related to inhibiting NR2B/CaMKIIα signaling pathway in preadolescent mice. Key words: Propofol; Liver; Reperfusion injury; Brain injuries; Infant; Receptors, N-methyl-D-aspartate; Calcium-calmodulin-dependent protein kinase type 2