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目的 通过观察UPAN对卵巢切除大鼠学习、记忆功能 ,海马神经元超微结构以及有关蛋白质表达的影响来证实UPAN对神经元退行性变有改善作用。方法 ♀大鼠 ,行双侧卵巢切除手术造模 ,并于 6wk后皮下注射UPAN进行治疗 ,12wk后行水迷宫实验 ,至 13wk开始行灌注固定 ,取脑组织作超薄切片进行电镜分析 ;作冰冻切片进行雌激素受体 (ERα)、糖元合成激酶 (GSK 3)、细胞周期动态激酶(CDK 5 )、蛋白磷酸酯酶 (PP 1、PP2A及PP 2B)免疫组化染色。结果 水迷宫检测卵巢切除组大鼠较正常组游完全程所须时间明显延长及错误反应次数明显增多 ,UPAN治疗组结果与正常组接近。去卵巢组大鼠海马神经元超微结构明显损害 ,ERα表达增高 ,GSK 3、CDK 5、PP 1、PP2A及PP 2B表达增高 ,但以蛋白激酶GSK 3和CDK 5增高最为明显。使用UPAN治疗后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 去卵巢大鼠存在着学习、记忆功能障碍 ,海马神经元超微结构以及有关蛋白质的表达出现异常改变。UPAN能明显改善其学习、记忆功能 ,维持海马神经元超微结构的完整性以及使有关蛋白质表达恢复到正常水平。
Objective To investigate the effects of UPAN on neurodegeneration in ovariectomized rats by observing the effects of UPAN on the learning and memory function, ultrastructure of hippocampal neurons and related protein expression in ovariectomized rats. Methods ♀ Rats were undergone bilateral ovariectomy and were treated subcutaneously with UPAN at 6 weeks after transplantation. Water maze test was performed after 12 weeks, and perfusion fixation was performed at 13 weeks. Ultrathin sections of brain tissue were taken for electron microscopy analysis. Frozen sections were used for immunohistochemical staining of ERα, GSK 3, CDK 5, PP 1, PP2A and PP 2B. Results Water maze test ovariectomized rats than the normal group of rats travel time was significantly longer and the number of false positives significantly increased, UPAN treatment group and the normal group close to the results. The ultrastructure of hippocampal neurons in ovariectomized rats was significantly damaged, the expression of ERα was increased, the expression of GSK 3, CDK 5, PP 1, PP2A and PP 2B were increased, but the increase of protein kinases GSK 3 and CDK 5 was the most obvious. The use of UPAN treatment can significantly improve the ultrastructural damage of hippocampal neurons, so that the expression of the above-mentioned protein returned to normal levels. Conclusion There are learning and memory dysfunction in ovariectomized rats, ultrastructural changes of hippocampal neurons and abnormal expression of related proteins. UPAN can significantly improve its learning and memory function, maintain the integrity of the ultrastructure of hippocampal neurons and restore the expression of related proteins to normal levels.