Effects of pretreatment with different doses of curcumin on expression of p-CREB and PGC-1α in hippocampus after global cerebral ischemia-reperfusion injury in rats / 中华麻醉学杂志

ABSTRACT

Objective To explore the effects of pretreatment with different doses of curcumm on the expression of p-CREB and PGC-1α in hippocampus after global cerebral ischemia-reperfusion (IR) injury in rats.Methods Three hundred male SD rats weighing 200-250 g were randomly divided 5 groups ( n = 60 each): sham operation group (group S), IR group, low, median and high dose curcumin group (group LC, MC, HC). Global cerebral ischemia was produced by occlusion of 4 vessels (cauterization of bilateral vertebral arteries and 15 min occlusion of bilateral common carotid arteries) according to the method described by Finkbeiner. Bilateral common carotid arteries were only exposed but not ligated in group S. Intraperitoneal curcumin 30, 100 and 300 mg/kg were injected at 1 h before ischemia in group LC, MC and HC respectively. Equal volume of dimethylsulfoxide (DMSO) was injected intraperitoneally in group S and IR. The rats were killed at 2, 6, 24 and 72 h and 7 d after reperfusion (12 at each time point). Brains were immediately removed and hippocampus was isolated. The number of apoptosis neurons was counted using TUNEL. The expression of p-CREB and PG C-1α protein in hippocampus was detected by Western blot. Results The number of apoptosis neurons, p-CREB and PG C-1α protein expression were significantly higher at each time point in the other 4 groups than in group S ( P ＜ 0.05). The number of apoptosis neurons was significantly lower at T2-4 in group LC and MC, while p-CREB and PG C-Ⅰα protein expression wes significantly higher at T1-4 in group LC, MC and HC than in group IR (P ＜ 0.05). The number of apoptosis neurons was significantly higher, while p-CREB and PGC-1α protein expression was significantly lower at T2-4 in group LC and HC than in group MC ( P ＜ 0.05). Conclusion Curcumin can inhibit neuronal apoptosis in hippocampus and reduce global cerebral IR injury by up-regulating p-CREB and PG C-1α expression in rats and the effect was dose-related.