雌激素与山核桃油干预对去卵巢大鼠海马早老基因-1与载脂蛋白E基因表达的影响

Intervention Effect of Estrogen Combined with Pecan Oil on the Gene Expressions of Alzheimer gene-1 and Apolipoprotein E Gene in Ovariectomized Rat Hippocampus

目的:观察雌激素干预后,核桃油对去卵巢大鼠海马组织早老基因-1(PS-1)与载脂蛋白E(aproE)基因表达及匀浆液中β淀粉样肽(Aβ)含量的变化。探讨核桃油对PS-1、aproE表达的调节与雌激素(E2)间的关系。方法:以去卵巢雌性大鼠为动物模型,实验组灌胃给予核桃油100mg/(kgbw·d)(低剂量组)、200mg/(kgbw·d)(中剂量组)、400mg/(kgbw·d)(高剂量组)(n=16)。空白组给予相同剂量的生理盐水。各组一半的大鼠随机接受E2处理,采用RT-PCR检测大鼠海马PS-1与aproE基因表达,RIA检测海马Aβ的含量的变化,放免法测血清E2水平。结果:雌激素干预的模型鼠血清E2水平显著高予未干预组(P<0.01);海马Aβ含量空白组最高,随核桃油剂量增加Aβ含量逐渐下降,中、高剂量组更显著(P<0.05),E2干预后Aβ含量下降更明显;空白组PS-1的表达最高而apoE的表达最低,随核桃油剂量增加各剂量组PS-1的表达仅轻度下降,apoE-mRNA表达明显增加;雌激素干预后PS-1的表达有所下降,apoE基因各组间表达差异消失。结论:E2和核桃油都可以通过降低去卵巢大鼠海马的PS-1基因及增加aproE基因的表达来降低Aβ的水平;但二者对PS-1基因调节可能通过不同的途径实现,而对apoE基因可能通过相同的途径来调节。

Objective：To study the effect of pecan oil on the serum estrogen（E2） level and gene expressions of Alzheimer gene-1（PS1） and apolipoprotein E（aproE） gene and Aβ content in the hippocampus of ovariectomized rats subjected to E2 intervention.Methods：Ovariectomized female rats were used as animal model and divided into 8 groups for 8 rats in each group：groups given low dose（100 mg/kg） pecan oil alone or plus E2,separately named low-dose pecan oil group and low-dose pecan oil plus E2 group,middle-dose pecan oil group and middle-dose pecan oil plus E2 group and high-dose pecan oil group and high-dose pecan oil plus E2 group obtained similarly,control group（given only saline） and E2 group（given only E2）.RT-PCR was used to detect the gene expressions of PS-1 and aproE in rat hippocampus,and radioimmunoassay to detect the level of Aβ in rat hippocampal and serum E2 level.Results：E2 intervention resulted in a significant（P0.01） increase in serum E2 level in ovariectomized rats.The highest Aβ level was observed in the control group.Regardless of whether or not E2 intervention was adopted,Aβ level gradually decreased with increasing pecan oil dosage and a significant difference（P0.05） was observed within both middle and high dose groups.The presence of E2 resulted in a large decrease in Aβ level in comparison with the control group,which exhibited the highest PS-1 gene expression but the lowest aproE gene expression.For rats both with and without E2 intervention,PS-1 gene expression showed only a slight decrease with increasing pecan oil dosage,while aproE gene expression markedly increased.However,at the same pecan oil dosages,E2 intervention resulted in a slight decrease in PS-1 gene expression but did not affect.The differences in aproE gene expression among these three pecan oil dosage groups disappeared.Conclusion：Both E2 and pecan oil PS-1 can attenuate PS-1 gene expression and elevate aproE gene expression so as to reduce Aβ level.Their regulatory effects on PS-1 gene might be achieved by different pathways;however,the same pathway seem to be used by them to regulate aproE gene.