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叶酸对AD炎症小鼠脑内Flotillin-1及Aβ表达的影响

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目的 观察叶酸(folic acid,FA)补充对炎症刺激AD小鼠脑内Flotillin-1及β淀粉样蛋白(β-amyloid protein,Aβ)代谢相关蛋白表达的影响。方法 27 只 6 月龄雄性APP/PS1 小鼠,随机分为AD组、AD+LPS组和AD+LPS+FA组,每组各9 只。9 只同月龄C57BL/6J雄性小鼠作为野生对照(Control)组。给予AD+LPS+FA组叶酸补充饲料(8 mg/kg)干预 3 个月,其他3 组喂养普通饲料。实验结束前1 周对AD+LPS组与AD+LPS+FA组小鼠腹腔注射脂多糖溶液(LPS,250 μg/(kg·d)),其余两组注射生理盐水。采用ELISA方法检测各组小鼠血清炎症因子TNF-α、IL-6含量以及脑组织Aβ1-40、Aβ1-42 水平,Western blot检测脑组织Flotillin-1 蛋白的表达,免疫荧光双标法检测脑皮质区Flotillin-1和Aβ1-42/APP/PS1/BACE1 的共表达。结果 经方差分析,与Control组相比,AD组小鼠血清TNF-α、IL-6含量升高(P<0。05)、脑内Aβ1-40 和Aβ1-42 水平升高(P<0。05)、脑内Flotillin-1蛋白的表达增加(P<0。05)、脑组织皮质区Flotillin-1与Aβ1-42/APP/PS1/BACE1 的共表达蛋白增多(P<0。05);与AD组相比,AD+LPS组小鼠血清炎症因子和脑内Aβ水平均进一步升高(P<0。05)、脑组织皮质区Flotillin-1与Aβ1-42/APP/BACE1 双标阳性蛋白表达量增多(P<0。05);与AD+LPS组相比,AD+LPS+FA组小鼠体内炎症水平和脑内Aβ含量降低(P<0。05)、脑组织Flotillin-1蛋白表达减少(P<0。05)、脑组织皮质区Flotillin-1与Aβ1-42/APP/PS1/BACE1 蛋白的共表达量减少(P<0。05)。结论 补充叶酸能够降低AD炎症小鼠脑内Flotillin-1蛋白的表达,减少Aβ沉积。
Effect of folic acid on the expression of Flotillin-1 and β-amyloid protein in the brain of mice with Alzheimer's disease inflammation
Objective To observe the effects of folic acid(FA)supplementation on the expression of Flotillin-1 and β-amyloid protein(Aβ)-metabolism-related proteins in the brains of inflammation-stimulated Alzheimer's disease(AD)mice.Methods Twenty-seven 6-month-old male APP/PS1 mice were randomly divided into AD,AD+LPS,and AD+LPS+FA groups,with nine mice in each group.Nine C57BL/6J male mice born within the same month were used as the Control group.The AD+LPS+FA group was given folic-acid-supplemented feed(8 mg/kg)for 3 months of intervention,while the other three groups were fed normal feed.Lipopolysaccharide solution(LPS,250 μg/(kg·d))was injected intraperitoneally into mice in the AD+LPS and AD+LPS+FA groups 1 week before the end of the experiment,and saline was injected into the remaining two groups.The serum inflammatory factors TNF-α and IL-6 levels and brain tissue Aβ1-40 and Aβ1-42 levels of mice in each group were detected by ELISA.Flotillin-1 protein expression in brain tissue was detected using Western blot,and the co-expression of Flotillin-1 and Aβ1-42/APP/PS1/BACE1 in the cortical region of the brain was detected via immunofluorescence double-labeling.Results After ANOVA analysis,we found mice in the AD group had elevated serum TNF-α and IL-6 levels(P<0.05),elevated levels of Aβ1-40 and Aβ1-42(P<0.05),increased expression of Flotillin-1 protein(P<0.05),and increased co-expression of Flotillin-1 and Aβ1-42/APP/PS1/BACE1 in the cortical brain tissue(P<0.05)compared with the Control group.Compared with mice in the AD group,those in the AD+LPS group had further increases in serum inflammatory factors and Aβ levels in the brain(P<0.05)and increased co-expression of Flotillin-1 and Aβ1-42/APP/BACE1 double-labeled proteins in their cortical brain tissue(P<0.05).Compared with mice in the AD+LPS group,those in the AD+LPS+FA group had lower in vivo inflammation levels and Aβ content in the brain(P<0.05),lower brain tissue Flotillin-1 protein expression(P<0.05),and lower Flotillin-1 and Aβ1-42/APP/PS1/BACE1 protein co-expression in cortical brain tissue(P<0.05).Conclusions Folic acid supplementation may reduce Flotillin-1 protein expression and Aβ deposition in the brain of AD inflammatory mice.

folic acidβ-amyloid proteinFlotillin-1Alzheimer's diseaseinflammation

马泽微、黄丽、郑云勤、张美琳、刘欢

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天津医科大学公共卫生学院营养与食品卫生学系,天津 300070

人群重大疾病防控教育部重点实验室,天津 300070

天津市环境营养与人群健康重点实验室,天津 300070

叶酸 β淀粉样蛋白 Flotillin-1 阿尔茨海默病 炎症

国家自然科学基金

82173516

2024

中国比较医学杂志
中国实验动物学会,中国医学科学院医学实验动物研究所

中国比较医学杂志

CSTPCD北大核心
影响因子:0.473
ISSN:1671-7856
年,卷(期):2024.34(8)