雌激素对双侧穹隆-海马伞切断及去势大鼠脑源性神经营养因子表达的影响

Effect of estrogen on the expression of brain-derived neurotrophic factor in rats with bilateral hippocampal fimbria-fornix transection and ovariectomy

目的 采用双侧穹隆-海马伞切断及双侧卵巢切除方法制作大鼠认知障碍模型,观察4个脑区脑源性神经营养因子(BDNF)表达的变化,以及补充外源性雌激素对BDNF的影响。方法选择健康雌性Wistar大鼠30只,先按2×2方差分析设计分别建立4个模型组:穹隆-海马伞切断组(FF组)、卵巢切除组(OVX组)、卵巢切除加穹隆-海马伞切断组(OF组)和对照组,然后再建立OF组同时给予雌二醇(E2 )治疗组(OF+E2 组)和双侧穹隆-海马伞切断加卵巢切除对照组,每组5只。E2 剂量为1mg/kg,每7天1次皮下注射,共4次28天。观察各组大鼠海马CA1区、皮质区、杏仁复合体区、基底前脑Meynert核区BDNF蛋白表达的变化。结果 (1)经F分析,双侧卵巢切除和双侧穹隆-海马伞切断与否存在主效应和显著交互效应(P<0 001)。FF组、OVX组和OF组的BDNF阳性细胞计数在海马CA1区、皮层、杏仁复合体、Meynert核均明显少于对照组(P<0 001),其中OF组在Meynert核区的BDNF阳性细胞计数少于FF组和OVX组(P<0 01); (2)OF组+E2 组在4个脑区的BDNF阳性细胞数均多于OF对照组(均P<0 01和<0 05)。结论 双侧穹隆-海马伞切断和(或)双侧卵巢切除均可导致大鼠脑内BDNF表达减少,补充外源性雌激素可显著增加BDNF的表达。

Objective To observe the expression of brain-derived neurotrophic factor (BDNF) in four brain areas of rats with the bilateral fimbria-fornix transection and ovariectomy, and with the estrogen replacement therapy.Methods The experiment was a 2×2 factorial design. Thirty Wister female rats were randomly divided into 4 model groups: fimbria-fornix transection (FF) group, ovariectomy (OVX) group, fimbria-fornix transection combined with ovariectomy (OF) group, and control group. The brain bilateral fimbria-fornix was transected in the stereotaxic apparatus. Secondly, estrogen replacement therapy model (OF+E 2 group) was made by treating the OF rats with the estradiol (1 mg/kg) once a week for 28 days. Immunoreactive cells of BDNF in the hippocampus CA1, cerebral cortex, amygdaloid complex and Meynert nucleus were measured with immunohistochemical way.Results Bilateral fimbria-fornix transection and ovariectomy had an interaction on the expression of BDNF in the four areas (P<0.001). The expression of BDNF remarkably decreased in hippocampus CA1, cerebral cortex, amygdaloid complex and Meynert nucleus in rats with the bilateral fimbria-fornix transaction (F=281.834-649.959, P<0.001) or ovariectomy (F=260.035-943.254, P<0.001), and the most marked decrease in Meynert nucleus area was in rat with ovariectomy combined with fimbria-fornix transection (F=17.505, P<0.01). The expression of BDNF was significantly higher in the OF+E 2 group than that in the OF control group (t=5.961-20.091, P<0.01).Conclusions The results indicate that the bilateral fimbria-fornix transection and ovariectomy decrease the expression of BDNF. The estrogen replacement therapy may be a useful way of improving the expression of BDNF.