摘要
目的:观察不同时期阿尔茨海默病(AD)小鼠脑中促性腺激素释放激素(GnRH)表达的变化,探讨其与AD的内在关系。方法:140只昆明鼠随机分为对照组和AD模型组,每组又按取样时间不同分为0、15、30、45、60、75和90d七个亚组,每亚组10只。采用D-半乳糖联合氯化铝构建AD小鼠模型,跳台实验观察各组小鼠认知功能;Westernblot法测定海马苏氨酸231位点磷酸化tau蛋白(Tau-pThr231)水平;ELISA法测定血清中雌二醇(E2)水平;免疫组化观察脑组织中GnRH的表达。结果:AD模型组45、60、75、90d小鼠的认知功能减退,Tau-pThr231表达增高(P<0.05),其中60、75、90d的AD模型组小鼠GnRH水平低于对照组(P<0.01),90d的AD模型组小鼠E2水平低于对照组(P<0.05)。结论:GnRH表达与AD的严重程度正相关,GnRH表达减少可能是比雌激素更早影响AD发病的因素。
Objective To study expression changes of gonadotropin releasing hormone （GnRH） in Alzheimer＇s disease mice at different periods and analyze their relationship with AD. Methods Mice were randomly divided into 2 groups： control group （n = 70）, AD model group （n = 70）. Each groups were divided into 7 subgroups （n = 10） according to different days （0, 15, 30, 45, 60, 75 and 90 d）.AD model mice were made by D-galactose and aluminum chloride. The ability of learning and memory in mice were observed by step-down test. The level of estrogen in serum was measured by ELISA. And the expression of Tau-pThr231 and GnRH were detected by Western Blot and immunohistochemistry. Results Compared with the control group, AD model miee at the 45th, 60th, 75th, 90th days showed a significant decrease in the learning and memory abilities （P 〈 0.05）, and the expression of Tau-pThr231 increased at the same time. The level of GnRH in brains of AD model mice was significantly decreased compared with control group （P 〈 0.01 ） at the 60th, 75th, 90th days. The level of estrogen in serum in AD model mice was obviously lower than that in control group at the 90th day （P 〈 0.05）. Conclusions The results suggested that there was positive correlation of GnRH with severity of AD. The decreased expression of GnRH may be one of the risk factors of AD, happened earlier than estrogen.
出处
《实用医学杂志》
CAS
北大核心
2011年第20期3656-3659,共4页
The Journal of Practical Medicine
基金
珠海市科技计划项目(编号:PC20052013)
关键词
阿尔茨海默病
GNRH
雌二醇
TAU蛋白磷酸化
认知功能
Alzheimer＇s disease
Gonadotropin releasing hormone
Estrogen
Tau protein phosphorylation
Cognitive function
