摘要
目的探讨雌激素对淀粉样β蛋白(Aβ1-40)诱导大鼠海马神经元Nogo-A和Nogo受体表达变化的影响。方法于雄性SD大鼠双侧海马注射Aβ1-40,颈部皮下植入可持续释放60d的17β-雌二醇片剂(E2),60d后取脑行冰冻切片,采用抗Nogo(N-18)多克隆抗体和Nogo受体抗体免疫组织化学染色法和免疫阳性细胞计数法检测Nogo-A和Nogo受体表达变化。结果正常大鼠海马和大脑皮质神经元胞核Nogo(N-18)免疫反应呈强阳性;海马CA1区可见深染的Nogo受体阳性反应神经元广泛分布,胞质、胞核内有棕黄色阳性反应颗粒。与正常对照组比较,阿尔茨海默病(AD)模型组Nogo-A免疫阳性细胞数明显增多;海马Nogo受体阳性反应细胞着色浅,少有突起,细胞数减少。E2处理组Nogo-A的表达量降低和Nogo受体表达量升高均与正常对照组相似。安慰剂处理组Nogo-A的表达量和Nogo受体染色结果与AD模型组相似。结论AD大鼠海马神经元存在着Nogo-A表达上调和Nogo受体表达下调,可能与AD的病理改变有一定的联系。雌激素可使上述二者恢复至正常水平,对AD有一定治疗作用,其作用机制尚需进一步探讨。
Objective To observe the effect of the estrogen on the expressions of Nogo-A and Nogo-receptor in hippocarnpus induced by Aβ1- 40. Methods The Alzheirner＇s disease （AD） male rats were established after injecting Aβ1-40 into bilateral hippocarnpus and laying aside a pump containing estrogen in the subcutaneous tissue of neck to release estrogen for 60 days. We observed the expressions of Nogo-A and Nogo-receptor in hippocarnpus of rats and quantitative analysis was performed after all sections were treated by the irnnrnunohistochemical staining. Results The nuclei of neurons expressed Nogo（N-18） strongly in hippoeornpus and cerebral cortex of control rats. The neurons with Nogo-receptor were widely distributed in CA1 area of hippocampus and cerebral cortex of control rats. The number of Nogo-A positive neurons in AD rats were significantly more than those in control rats, but the neurons with Nogo-receptor in the hippocampus decreased obviously. However, the expression of Nogo-A downregulated and Nogo-receptor upregulated in rats treated by 17β-estradiol （E2）, bui no significant difference were observed between the group with 17β-estradiol（E2 ） and controls. The expressions of Nogo-A and Nogo-receptor in control groups were similar to those in AD groups. Conclusion The Nogo-A upregulation and Nogo-receplor downregulation in AD rats have relationship with the pathological changes. The estrogen can normalize the expressions of Nogo-A and Nogo-receptor so that estrogen can protect neurons frorn damages. The rnechanisrn of Nogo-A upregulation and Nogo receptor downregulation induced by estrogen in AD models need the further research. Nogo-A and Nogo-receptor are presumed to be involved in the pathological processes of AD.
基金
湖北省教育厅重点科研项目(B200624005)
郧阳医学院基础医学院学生科研项目(2006xsky01)
郧阳医学院基础医学院2005年度科研项目(2005ky02)
