长期口服复方尼尔雌醇和小剂量17β-雌二醇对去卵巢大鼠海马结构内脑源性神经营养因子表达的影响

Effects of long-term replacement therapy of compound nylestriol tablet or low-dose 17 beta-estradiol on expression of brain-derived neurotrophic factor in OVX rat hippocampal formation

目的观察长期雌激素缺乏大鼠海马结构内脑源性神经营养因子(brain-derivedneurotrophicfac-tor,BDNF)表达的变化,同时观察比较长期口服小剂量17β-雌二醇和复方尼尔雌醇对去卵巢大鼠海马结构内BDNF表达的作用及效果。方法7月龄SD大鼠按体重随机分成5组:正常对照组(Normal,NORM)、假手术组(Sham-ovariectomy,SHAM)、去卵巢组(Ovariectomy,OVX)、17β-雌二醇预防干预组(Preventiveinterven-tionby17β-estradiol,OVX/ERT)和复方尼尔雌醇预防干预组(Preventiveinterventionbycompoundnylestri-ol,OVX/NL)连续观察。5组均在去卵巢后35周处死。用免疫组织化学的方法(SABC法)显示大鼠海马结构内BDNF的表达,细胞计数及图象分析法观察去卵巢大鼠海马结构内BDNF表达的变化。结果OVX组海马结构内各亚区BDNF阳性神经元较少。OVX组海马结构内各亚区BDNF阳性神经元数量、平均光密度均低于NORM组、SHAM组、OVX/ERT组和OVX/NL组(P<0.05)。结论长期雌激素缺乏导致了大鼠海马结构内BDNF表达的下降,长期口服小剂量17β-雌二醇和复方尼尔雌醇补充治疗有利于去卵巢大鼠海马结构内神经元BDNF的正常表达,从而发挥雌激素的神经营养作用。复方尼尔雌醇获得了与小剂量17β-雌二醇相同的效果。

To determine the effects of long-term estrogen deficiency and replacement therapy of compound nylestriol tablet or low-dose 17 beta-estradiol on the expression of brain-derived neurotrophic factor (BDNF) in rat hippocampal formation. Fifty seven-month-old female Sprague-Dawley rats were randomly divided into five groups: Normal (NORM), Sham-ovariectomy (SHAM), Ovariectomy (OVX), Preventive intervention by 17β-estradiol (OVX/ERT) and Preventive intervention by compound nylestriol (OVX/NL). Immunohistochemistry of BDNF was used to quantitatively determine the levels of expression of BDNF using cell counting and imaging system in ovariectomized rat hippocampal formation. The numbers and optical density of BDNF-positive neurons of all hippocampal subregions and dentate gyrus in OVX rats were markedly lower than that of NORM, SHAM ,OVX/NL, and OVX/ERT rats, though no differences among NORM, SHAM, OVX/NL and OVX/ERT rats. [Conclusions] The data shows that long-term estrogen deficiency (OVX) can lead to decrease of BDNF expression in hippocampal formation while replacement of low-dose 17 beta-estradiol or compound nylestriol tablet can equally preserve the expression of BDNF to a normal level, showing neurotrophic effect of estrogen.