APP17肽对卵巢去势大鼠海马神经元退行性变的作用

THE EFFECT OF APP 17-MER PEPTIDE ON NEURODEGENERATION OF HIPPOCAMAL NEURONS IN OVARIECTOMIZED RATS

目的 通过观察APP17肽对卵巢去势大鼠海马神经元退行性变的作用 ,证实APP17肽对神经元退行性变的改善作用。 方法 雌性大鼠 ,行双侧卵巢切除手术造模 ,并于 6周后皮下注射APP17肽进行治疗 ,手术后12周行水迷宫实验 ,至 13周取血并行灌注固定 ,取脑海马组织作超薄切片电镜分析 ,并作冰冻切片进行雌激素受体 (ERα)、神经生长因子 (NGF)及脑源性神经生长因子 (BDNF)免疫组织化学染色 ,并用全自动化学发光免疫分析仪测定血清雌二醇水平。 结果 卵巢去势组大鼠血清雌二醇水平降低 ,水迷宫检测卵巢去势组大鼠较正常组游完全程所须时间明显延长 ,错误反应次数明显增多 ,海马神经元超微结构出现明显损害 ;海马光镜观察发现ERα表达增多 ,NGF及BDNF表达减少。使用APP17肽治疗后并不改变血清雌二醇水平 ,但能明显改善海马神经元超微结构的损害 ,使上述有关蛋白质的表达恢复到正常水平。 结论 APP17肽不是通过改变雌激素水平来发挥改善神经元功能减退的作用 。

Objective To study the neurotherapeutical effects of APP17 peptide on neurodegeneration in hippocampal neurons. Methods Adult rats were bilaterally ovariectomized, and APP17 mer peptide was injected after six weeks as a curative. APP17 mer peptide was synthesized by solid phase method in our laboratory and purified by HPLC. Twelve weeks later, water maze testing of behavior was conducted; then fixative was injected into the rats. Tissue specimens for each group were removed from the hippocampus CA1 area for electron microscopy studies; cryostat sections were studied by immunohistochemistry for ERα、NGF and BDNF. Results 1 OVX group had low blood estradiol level, and App 17\|mer peptide injection did not change its level. 2 Results of water maze test; Full\|course swimming time was clearly longer in OVX Group, and the number of errors committed higher. In the use of APP 17\|mer peptide, the results were similar to Grop C. 3 The hippocampal ultrastructure has abnormal change. in the use of APP17 peptide, it can cotain the integrity of hippocampal ultrastructure. 4 In group OVX, the expression of NGF、BDNF is reduced; the expression of ERα is increased. APP17 peptide can normalize expression of proteins as above. Conclusion\ APP17 peptide can improve the neurodegeneration not as estrogen but as neurotrophin.\;[