中文摘要：

探讨慢性高同型半胱氨酸血症对老年大鼠脑内tau蛋白结构和功能的影响以及其可能机制。方法：选取18月龄健康大鼠，尾静脉注射同型半胱氨酸（Hcy）生理盐水溶液（1．6mg·kg-·d“）制造高同型半胱氨酸血症模型组，在给予Hcy的同时通过饮用水给予叶酸（4mg·kg-1·d“）和维生素B。：（VitB12,250g·kg-1·d“）作为治疗组，单纯注射生理盐水作为对照组，持续28周，Bielschowsky银染观察磷酸化tall蛋白的分布和聚集；Westernblotting检测磷酸化tau蛋白、糖原合酶激酶3B（GSK-3p）和蛋白磷酸酶2A（PP2A）的表达。结果：（1）血浆中Hcy水平增高导致神经原纤维样缠结；给予叶酸和VitB12能够有效减轻缠结；（2）血浆高Hey水平诱导老年大鼠脑内tau蛋白在ser199/202”和Ser396位点磷酸化水平升高；（3）血浆高Hey水平激活GSK-3B同时抑制PP2A的活性。补充叶酸和VitB，：有效地缓解了这些激酶和酯酶的活性改变，并下调了tau蛋白Ser“”和ser”位点的磷酸化水平。结论：补充叶酸和VitB，：能够有效改善高同型半胱氨酸血症所诱导的tau蛋白阿尔茨海默样病理改变，其机制可能与其抑制GSK一3B活性和激活PP2A有关。

英文摘要：

To explore the effect of hyperhomocysteinemia on the Alzheimer- like pathological changes in the brain of aged rat. METHODS： The rats were treated with homocysteine （Hcy） by intravenous injection through ve- na caudalis with or without a simultaneous supplementation of folate and Vitamin Bt2 （FB） in the drinking water for 28 weeks. The distribution and aggregation of tan protein were detected by Bielschowsky silver staining. Western blotting was used to determine the protein levels of tan phosphorylation, glycogen synthase kinase 313 （ GSK - 313） and protein phospha- tase 2A （PP2A）. RESULTS： Treatment with Hcy induced hyperhomocysteinemia in aged rats and resulted in the forma- tion of neurofibrillary tangles in the brain. Supplementation of FB effectively reduced the tangles. Hyperhomocysteinemia also induced Alzheimer -like tan hyperphosphorylation at multiple sites （Ser199/202and Ser396）. Hyperhomocysteinemia acti- vated GSK- 313 and inhibited the activity of PP2A. Supplementation of FB alleviated the changes of tan and the activities of GSK -313 and PP2A. CONCLUSION： Supplementation of FB ameliorates the hyperhomocysteinemia -induced Alzheimer -like pathological changes of tau protein possibly through regulating the activity of GSK-313 and PP2A in aged rats.