17β雌二醇对氯胺酮诱导发育期大鼠神经细胞凋亡的影响

17β-estradiol protects against ketamine-induced neuroapoptosis in the developing rat brain

目的探讨17β雌二醇对氯胺酮诱导发育期大鼠额叶皮层区神经细胞凋亡的影响。方法 30只7日龄雄性SD幼鼠,随机均分为对照组(C组)、氯胺酮组(K组)和氯胺酮+17β雌二醇组(KE组),每组10只。K组连续3d腹腔注射氯胺酮75mg/kg,KE组连续3d腹腔注射氯胺酮75mg/kg,同时皮下注射17β雌二醇600μg/kg,C组连续3d腹腔注射等容量生理盐水。末次注药后24h,取额叶皮层应用免疫组化法检测cleaved-caspase-3的阳性表达量,同时应用Western blot法检测pAkt以及pGSK-3β蛋白的表达量。结果与C组比较,K组皮层区cleaved-caspase-3阳性和pGSK-3β蛋白的表达量明显增加,pAkt蛋白的表达量明显下降(P<0.01);与K组比较,KE组皮层区cleaved-caspase-3阳性和pGSK-3β蛋白的表达量明显下降,pAkt蛋白的表达量明显增加(P<0.01)。结论 17β雌二醇可对氯胺酮诱导的发育期大鼠大脑皮层区神经细胞凋亡产生保护作用,其机制可能与增加pAkt蛋白的表达同时降低pGSK-3β蛋白的表达有关。

Objective To investigate the effect of 17β-estradiol on ketamine-induced neuroapop tosis in neonatal rats. Methods Thirty SD male rats, aged 7 days, were randomly divided into group C, K and KE （10 in each group）. Group K and group KE were intraperitoneally injected with 75 mg/ kg ketamine for three consecutive days; in addition 600 μg/kg 1713-estradiol was injected subcutaneously for three consecutive days to group KE; group C received same volume of intraperitoneal saline as control. 24 hours after the last injection, five rats from each group were decapitated under deep anesthesia and the PFC （prefrontal cortex） portion was isolated to detect cleaved caspase-3 by immunohistochemical analysis. The PFC of other rats was harvested to determine pAkt and pGSK-3β by western-blot. Results Compared with group C, the expression level of cleaved caspase-3 and pGSK 3β increased, while pAkt level reduced significantly in group K （P〈0.01）. Compared with group K, the expression of cleaved caspase-3 and pGSK-3β reduced significantly, while pAkt level increased significantly in group KE （P〈0. 01）. Conclusion 17β-estradiol protects against ketamine-induced neuroapoptosis in the developing rat brain, which is associated with the increase level of pAkt and the decrease level of pGSK-3β.