摘要
目的探讨莱菔硫烷(SFN)对阿尔茨海默病(AD)模型小鼠学习记忆和胆碱能系统的影响,为防治AD提供理论依据。方法健康成年C57BL/6J小鼠按体重随机分为3组,每组18只,雌雄各半。模型组和干预组小鼠饮用含铝水(浓度为0.4 g/100 ml),并隔日皮下注射200 mg/kg D-半乳糖,此外,干预组小鼠每日1次灌胃给予25 mg/kg SFN,模型组小鼠每日1次灌胃等量蒸馏水,同时设立溶媒对照组。每日1次观察小鼠的一般状况,并每周称重1次,90 d后采用跳台实验测定小鼠的学习记忆能力,石墨炉原子吸收光谱法测定脑组织铝含量,乙酰胆碱转移酶(ChAT)免疫组化法观察海马CA1区胆碱能神经元丢失情况,分光光度计法测定大脑皮层乙酰胆碱(Ach)含量、乙酰胆碱酯酶(AChE)和ChAT活性,Real-time PCR法检测大脑皮层ChAT mRNA的表达。结果在整个受试期间各组小鼠均未见异常表现及死亡,各组小鼠体重差异无统计学意义(P>0.05)。与对照组相比,模型组小鼠学习记忆能力下降(P<0.01),脑铝含量增高(P<0.01),海马CA1区胆碱能神经元细胞数减少(P<0.05)。与模型组相比,SFN能提高小鼠的学习记忆能力(P<0.01),降低脑铝含量(P<0.01),增加海马CA1区胆碱能神经细胞数(P<0.05)。此外,干预组小鼠脑铝含量高于对照组(P<0.01),大脑皮层ChAT mRNA水平低于对照组和模型组(P<0.05);各组小鼠大脑皮层Ach含量、AChE和ChAT活性差异无统计学意义(P>0.05)。结论 SFN可明显减少AD模型小鼠胆碱能神经元的丢失,提高其学习记忆能力。
Objective To investigate the effects of sulforaphane （SFN） on learning memory and cholincrgic system of Alzhei- mer＇s disease （AD） model mice and provide a theoretical basis for the prevention and treatment of AID. Methods Healthy adult C57BL/6J mice were randomly divided into three groups according to their body weight, with 9 male and 9 female mice for each group. The mice in the model and intervention groups were administered with drinking water containing 0.4g/100ml alumi num acl libitum and subcutaneously injected with 200mg/kg D galactose every other day. In addition, the mice in the interven- tion and model groups were respectively treated with 25 mg/kg SFN and equivalent distilled water by a single oral gavage daily. Meanwhile, the mlvent control group was established. The mice was observed daily and weighed each week. After 90 days, the learning memory ability of the mice was measured by step down test and the aluminum in the brain was detected by graphite furnace atomic abmrption spectrophotometry. The expressions of ChAT protein in CA1 subfield of hippocampus and ChAT mR- NA in the cerebral cortex of mice were examined by inmmnohistochemisty and real - time PCR, respectively. And the Ach levels and AChE and ClOT activities in the cerebral cortex were measured by colorimetric method. Results No animals behaved abnormally and died, and no significant difference was found in the body weight of the mice among the groups during the experi- ment （P〉0.05）. Compared to the control group,the aluminum level in the mice brain of AD model group was remarkably in- creased （ P 〈 0.01 ）, and the learning memory ability and cholinergic neurons in the CA1 subfield of hippocampus significantly de creased （P 〈 0.01 and P 〈 0.05, respectively）. Compared to AD model group, SFN could decrease the brain aluminum level（P 〈 0.01 ）, improve the learning memory ability（ P 〈 0.01 ）and increase the cholinergic neurons in the CA1 subfield of hippocam- pus （P〈0.05）. The brain aluminum level in the AD model mice treated with SFN was higher than that of the contn）l （P〈 0.01 ）, and the ChAT mRNA expression was lower than thc,se of the control and AD mcvlel mice （P 〈 0.05）. No significant dif ference was found in Ach levels, AChE and ChAT activities in the cerebral cortex of mice among the groups （ P 〉 0.05 ）. Conclusions SFN can protect cholinergic neurons from damage and improve the learning memory ability in AD model mice.
出处
《实用预防医学》
CAS
2014年第2期163-167,共5页
Practical Preventive Medicine
