雌激素对全脑缺血再灌小鼠海马CA_1区P-CREB和BDNF表达的影响

本文观察了雌激素对全脑缺血再灌的影响并探讨了其作用机制。切除小鼠双侧卵巢同时于颈部皮下植入雌激素(E2)缓释片(OVXE2组)或安慰剂缓释片(OVXPLC组)。术后18d,手术暴露双侧颈总动脉并夹闭25min后再通,制作全脑缺血再灌模型,分别于灌流后1h,12h,3d,7d取材进行PCREB和BDNF免疫组化染色和常规Nissl染色,研究E2对雌性小鼠全脑缺血/再灌流损伤后海马CA1区PCREB和BDNF表达的影响。结果表明:缺血再灌后7d,OVXPLC组海马CA1区神经元排列稀疏,细胞层次减少,细胞数低于OVXE2组(P<0.01);在缺血再灌后3d,OVXPLC组海马CA1区PCREB阳性细胞数低于OVXE2组(P<0.01),而BDNF的表达无统计学差异(P>0.05);在缺血再灌后7d,OVXPLC组PCREB和BDNF的表达均低于OVXE2组(P<0.01)。以上实验结果提示,E2在缺血再灌的中后期可能通过上调海马CA1区PCREB进而促进BDNF的表达,发挥神经元保护作用。

THE EFFECT OF ESTROGEN ON THE EXPRESSION OF P-CREB AND BDNF IN HIPPOCAMPAL CA1 OF KUNMING MICE FOLLOWING CEREBRAL ISCHEMIA/REPERFUSION

We examined the effect of estrogen on the brain protection after ischemia-reperfusion (IR) treatment and explored the underlying mechanisms. The mice received bilateral ovariectomy followed by subcutaneous placement of time release pellet containing either 17 beta-estradiol (E2, 1.7 mg, OVX-E2 group) or placebo (cholesterol, OVX-PLC group). On the 18 d of treatment, the common carotid arteries were occluded for 25 min and then had them reperfused. The animals were allowed to survive for different time spans (1 h, 12 h, 3 d, 7 d) and sacrificed for Nissl, P-CREB and BDNF immunohistochemistry staining. The results showed that 3 d after IR, the expression of P-CREB in hippocampal CA_1 region of OVX-E2 group was significantly higher than that of OVX-PLC group (P<0.01), but there was no difference in the expression of BDNF (P>0.05); 7 d after IR, the expressions of both P-CREB and BDNF were significantly higher than those of OVX- PLC group (P<0.01). These findings indicate that E2 may protect neurons in hippocampal CA_1 region via up-regulating the expression of P-CREB and subsequent to increase the expression of BDNF after cerebral ischemia.