AD模型小鼠脑组织AQP4、SNTA1表达水平的变化及DADS的干预研究  

CHANGES OF AQP4 AND SNTA1 EXPRESSION IN AD MODEL MICE BRAIN AND THE INTERVENTION OF DADS

作　　者：蒋聪敏 詹志鹏 张静竹 赵越 李玉婷 安丽 JIANG Cong-min;ZHAN Zhi-peng;ZHANG Jing-zhu;ZHAO Yue;LI Yu-ting;AN Li(Department of Nutrition and Food Hygiene,School of Public Health,China Medical University,Shenyang 110122;Department of Nutrition and Food Hygiene,School of Public Health,Jinzhou Medical University,Jinzhou 121001,China)

机构地区：[1]中国医科大学公共卫生学院营养与食品卫生学教研室,沈阳110122 [2]锦州医科大学公共卫生学院营养与食品卫生学教研室,锦州121001

出　　处：《营养学报》2018年第3期266-271,共6页Acta Nutrimenta Sinica

基　　金：辽宁省自然科学基金资助课题(No.20170541014)

摘　　要：目的探讨二烯丙基二硫化物(DADS)对阿尔茨海默病(AD)模型小鼠的干预作用,为AD的防治提供理论依据。方法将20只5月龄APPswe/PS1d E9双转基因鼠按窝别和体质量分为AD模型组和AD干预组,同时将野生型小鼠分为野生对照组和野生干预组,每组10只。干预组小鼠每日1次灌胃给予50 mg/kg DADS,AD模型组小鼠和野生对照组小鼠每日1次灌胃等量溶媒,连续处理6月。采用水迷宫和旷场实验测定小鼠神经行为学变化。免疫组化法分析大脑皮质β-淀粉样蛋白(Aβ)沉积情况,q RT-PCR和Western blot法分别检测大脑皮质水通道蛋白4(AQP4)、α-互养蛋白(SNTA1)m RNA及蛋白的表达水平。结果与对照组相比,AD模型组小鼠水迷宫实验中定位航行逃避潜伏期延长、穿越平台次数减少,在旷场实验中中央停留时间延长、穿格次数和直立次数减少,大脑皮质Aβ沉积数量增多,AQP4m RNA及蛋白表达升高,SNTA1m RNA及蛋白的表达水平下降,差异均有统计学意义(P<0.05或P<0.01)。与AD模型组相比,DADS干预组小鼠的定位航行逃避潜伏期缩短、穿越平台次数增多,中央停留时间缩短、穿格次数和直立次数增多,大脑皮质Aβ沉积数量减少,AQP4及SNTA1 m RNA及蛋白的表达水平上调,差异均有统计学意义(P<0.05或P<0.01)。结论 AD模型小鼠大脑皮质AQP4表达升高,但SNTA1表达的降低可改变AQP4极性分布而影响AQP4的功能。DADS可明显减少AD模型小鼠大脑皮质Aβ沉积,改善认知能力,其作用机制可能与DADS调节AQP4表达及其极性分布有关。Objective To investigate the effect of diallyl disulfide（DADS） on AD model mice and provide a theoretical basis for prevention and treatment of AD. Methods According to the nest and body weight,20 healthy APPswe/PS1 d E9 double transgenic positive mice were randomly divided into two groups（AD model and AD intervention, n= 10）; 20 healthy wild C57 BL/6 J mice were randomly divided into two groups（wild control and wild intervention, n = 10）. The mice in the AD intervention and wild intervention groups were gavaged with 50 mg/kg DADS once a day. The AD model and wild control groups were gavaged with an equivalent amount of oil.After 6 months, Morris water maze and open field were performed to investigate the change of neurobehaviour. Aβ depositions in the cerebral cortex of mice were detected by immunohistochemical method. QRT-PCR, Western blot were used to examine the expression of AQP4,SNTA1 m RNA and protein in the cerebral cortex of mice respectively. Results Compared to the control, there were significant decrease（P〈0.05） in cognitive ability, remarkable increase in the numbers of Aβ deposition（P〈0.05） and the expression of AQP4 m RNA and protein（P〈0.01 and P〈0.05, respectively）, and significant reduction（P〈0.01） in the expression of SNTA1 m RNA and protein in cerebral cortex of AD model mice. Compared with model group, DADS could improve the cognitive ability of AD model mice（P〈0.05）, decrease the cerebral cortex Aβ deposition（P〈0.05）, increase the expression of AQP4 and SNTA1（P〈0.01）.Conclusion There is an increase in the expression of AQP4 in the cerebral cortex of AD model mice, but a decrease in the expression of SNTA1 which influences the function of AQP4 by regulating its polarity distribution. DADS can reduce Aβ deposition, improve cognitive ability, and the mechanism may be associated with the alteration of AQP4 expression and its polarity distribution.

关 键 词：二烯丙基二硫化物 阿尔茨海默病 Β-淀粉样肽 水通道蛋白4 α-互养蛋白 

分 类 号：R151.2[医药卫生—营养与食品卫生学]