Abstract: Objective To investigate whether mitogen-activated protein kinases (MAPKs), which were involved in changes in osmolality, might mediate aquaporin-4 (AQP4) expression in astrocytes after oxygen-glucose deprivation (OGD) in rats. Methods Astrocytes were obtained from new born Sprague-Dawley rats. The P₂ cells were divided into control group, OGD group and inhibitors of U0126, SB203580 and SP600125 groups. The latter groups underwent OGD for five hours and reoxygenated, the inhibitors of U0126, SB203580 and SP600125 (1 μmol/L and 10 μmol/L, respectively) groups, named U1, U10, SB1, SB10, SP1 and SP10 groups, respectively, were cultured with the inhibitors for twelve hours. The volume of cells in OGD group was measured half, one, one and half, two, three, four, eight and twelve hours after reoxygenation, and the expression of AQP4 was detected half, one, one and half, eight and twelve hours after reoxygenation with Western blotting. The expression of AQP4, and phosphorylation of extracellular regulated protein kinases (p-ERK), c-Jun N-terminal kinase (p-JNK) and p38 MAPK (p-p38 MAPK) was detected 24 hours after reoxygenation in all the groups, while the activity of lactate dehydrogenase (LDH) was measured. Results The volume of cells increased in OGD group one and half, two, three and four hours after reoxygenation compared with those in the control group (P<0.001), and the expression of AQP4 also increased in OGD group after reoxygenation (P<0.001), especially 1.5 hours of reoxygenation. The expression of AQP4, p-ERK, p-JNK and p-p38 MAPK increased in OGD group after five hours of OGD compared with those in the control group (P<0.001), and the expression of p-ERK, p-JNK and p-p38 MAPK decreased in the inhibitors groups compared with those in OGD group (P<0.001), and the expression of AQP4 decreased in SB10 group (P<0.001). The activity of LDH was less in all the inhibitors groups except SP1 and SB1 groups than in OGD group (P<0.01), and was the least in SB10 group (P<0.001). Conclusion MAPKs signal pathway, especially p38 MAPK, may promote AQP4 expression in astrocytes after OGD in rat, and play a role in cells death.

Key words: oxygen-glucose deprivation, astrocyte, mitogen-activated protein kinases, signal pathway, aquaporin-4, edema, rats