摘要
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。
AIM To study the neuroprotective effects of UPAN on learning and memory function of ovariectonized rats by water maze test、ultrastructure and the expresson of protein in hippocampal neurons. METHODS Adult rats were bilaterally ovariectomized,and UPAN was injected after six weeks as a curative. UPAN was synthesized by solid phase method in our laboratory and purified by HPLC. Twelve weeks later, water maze testing of behavior was conducted; then the fixative was injected into the rats.Tissue specimens for each group were remored from the hippocampus CA1 area for electron microscopy studies;cryostat sections were studied by immunohistochemistry for ERα、GSK 3、CDK 5、PP 1、PP 2A and PP 2B. RESULTS (1) Water maze test found that 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 group C. (2)The hippocampal ultrastructure has abnormal change. In the use of APP17 peptide, it cotained the integrity of hippocampal ultrastructure. (3) In group OVX, the expresse of ERα、GSK 3、CDK 5、PP 1、PP 2A and PP 2B increased, but the increase of protein Kinase(GSK 3、CDK 5) was more obvious than protein phosphatase(PP 1、PP 2A and PP2B). CONCLUSION UPAN can improve the function of learning and memory of the rats,cotain the integrity of hippocampal ultrastructure and normalize expression of many protein, but it can not change the blood estradiol level.
出处
《中国药理学通报》
CAS
CSCD
北大核心
2001年第3期285-288,共4页
Chinese Pharmacological Bulletin
基金
北京市科委资助!项目
No 95 1890 60 0
