莱菔硫烷对阿尔茨海默病样损伤小鼠的神经保护作用  

Neuroprotective effect of sulforaphane in mice with Alzheimer's disease-like lesions

作　　者：周伏园 陈楠[2] 詹志鹏[1] 李心蕙 赵越[1] 安丽[1] 

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,辽宁沈阳110122 [2]辽宁中医药大学附属第四医院

出　　处：《实用预防医学》2016年第12期1428-1432,共5页Practical Preventive Medicine

基　　金：辽宁省教育厅科学研究一般项目(L2014289);辽宁省自然科学基金资助项目(2014021034)

摘　　要：目的探讨莱菔硫烷(SFN)对阿尔茨海默病(AD)样损伤小鼠的神经保护作用,为防治AD提供理论依据。方法健康成年C57BL/6J雄性小鼠按体重随机分为3组,每组10只。模型组和干预组小鼠饮用含铝水(浓度为0.4 g/100ml),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Morris水迷宫方法检测小鼠的认知能力,刚果红染色法检测脑组织老年斑(SP)沉积情况,Real-time PCR法检测大脑皮层Gβ2 mRNA水平,流式细胞术检测大脑皮质细胞内游离Ca^(2+)水平。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,模型组小鼠认知能力下降(P<0.05),大脑皮质及海马SP斑块数量均增多(P<0.01),大脑皮质Gβ2 mRNA水平降低(P<0.05),大脑皮质细胞内游离Ca^(2+)浓度升高(P<0.05)。与模型组相比,SFN能提高小鼠的认知能力(P<0.05),减少大脑皮质和海马SP斑块数量(P<0.01),提高大脑皮质Gβ2 mRNA水平(P<0.05),降低大脑皮质细胞内游离Ca^(2+)浓度。结论 SFN可明显减少AD模型小鼠脑组织SP沉积,改善认知能力,其作用机制可能与SFN调控G蛋白表达,防止细胞内钙超载有关。Objective To explore the neuroprotective effect of sulforaphane in mice with Alzheimer’s disease （AD）-like lesions so as to provide a theoretical basis for prevention and treatment of AD. Methods Thirty healthy male adult C57BL/6J mice were randomly divided into 3 groups based on their body weight, a control group, a model group and an intervention group, with 10 mice in each group. Mice in the model group and intervention group drank water containing aluminum （0.4 g/100 ml） ad libitum daily and were subcutaneously injected with D-galactose （200 mg/kg body weight） every other day, while the mice in the control group drank distilled water and received a subcutaneous injection of an equivalent amount of physiological saline instead. Besides, the mice in the intervention group were gavaged with 25 mg/kg SFN （perpared with distilled water） once a day, whereas the mice in the control group and the model group were gavaged with an equivalent amount of distilled water. The mice were observed daily for general condition and weighed each week. After 90 days, their spatial cognitive ability was evalated by morris water maze test.Senile plaque（SP） deposits in the brain was detected by congo red staining.The expression of G proten β2 subunit（Gβ2） mRNA and intracellular calcium level in the cerebral cortex were examined by real-time PCR assay and flow cytometry respectively. Results During the experiment, neither significant sign of toxicity nor death was observed in mice, and no statistically significant difference was found in the body weight of the mice among the three groups （P〉0.05）. Compared to the control group, the mice in the model group had a significantly decreased cognitive ability （P〈0.05） and remarkablely increased SP （P〈0.01） in both hippocampus and cerebral cortex, as well as attenuated Gβ2 mRNA expression and elevated intracellular calcium in the cerebral cortex （P〈0.05）. Compared with the model group, SFN could remarkably improve the mice’s cognitive imp

关 键 词：莱菔硫烷 阿尔茨海默病 G蛋白 钙超载 

分 类 号：R-332[医药卫生]