番茄红素对β-淀粉样蛋白诱导的脉络丛上皮细胞炎症损伤及TLR4信号通路的作用  

EFFECTS OF LYCOPENE ON INFLAMMATORY RESPONSE AND TLR4 PATHWAY OF CHOROID PLEXUS IN Β-AMYLOID INDUCED MODEL OF ALZHEIMER'S DISEASE

作　　者：刘重斌[1] 计涛 王利群[2] 易燕锋[1] 王瑞[1] 高喜仁[1] 

机构地区：[1]湖州师范学院医学院生理与药理学教研室,湖州313000 [2]吉安市第三人民医院,吉安343000

出　　处：《营养学报》2017年第5期489-493,共5页Acta Nutrimenta Sinica

基　　金：浙江省自然科学基金(No.LY15H260002);湖州市公益性应用研究项目(No.2016GY41);湖州市自然科学基金项目(No.2016YZ04)

摘　　要：目的探讨番茄红素对β-淀粉样蛋白诱导脉络丛上皮细胞炎症损伤的保护作用及可能机制。方法成年健康清洁级雄性SD大鼠40只,体质量(250±18.7g),随机分为空白对照、阿尔茨海默病(AD)模型、阿尔茨渊默病(AD)+番茄红素Ⅰ[ig.5 mg/(kg·d)]、AD+番茄红素Ⅱ[ig.10mg/(kg·d)]、番茄红素[ig.10mg/(kg·d)]共5组,每组8只。适应性饲养1w后,采用脑立体定位仪将8μg凝聚态Aβ1-42注入双侧大鼠海马区,建立AD动物模型。三个干预组连续灌胃番茄红素40 d,1/d。在造模后的第2、3、4、5w末进行水迷宫实验,评估大鼠学习记忆力。实验结束后,处死动物取血离心,ELISA法测定血清中TNF-α、IL-1β及IL-6β含量。RT-q PCR、Western blot法检测脉络丛上皮TLR4、NF-κB p65 mRNA、蛋白表达及海马神经元PS-1、β-APP mRNA、蛋白表达。结果神经行为结果显示,AD组大鼠平均逃逸时间及靶象限活动时间显著高于空白对照组(P<0.05),而番茄红素干预后,显著低于AD组(P<0.05)。血清中TNF-α、IL-1β及IL-6β含量结果显示,AD组大鼠TNF-α、IL-1β及IL-6β含量显著高于空白对照组(P<0.05),而番茄红素干预后,TNF-α、IL-1β及IL-6β含量显著降低(P<0.05)。脉络丛上皮TLR4、NF-κB p65 mRNA及蛋白表达结果显示,AD组大鼠TLR4、NF-κB p65 mRNA及蛋白表达显著高于空白对照组(P<0.05),而番茄红素干预后TLR4、NF-κB p65 mRNA及蛋白表达显著低于AD组(P<0.05)。海马神经元PS-1、β-APP mRNA及蛋白表达结果显示,AD组海马神经元PS-1、β-APP mRNA及蛋白表达显著高于空白对照组(P<0.05),而番茄红素干预后海马PS-1、β-APP mRNA及蛋白表达显著降低(P<0.05)。结论:番茄红素对β-淀粉样蛋白诱导脉络丛上皮炎症损伤有一定的保护作用,其作用机制可能通过脉络丛上皮TLR4信号通路,抑制炎症介质的产生,缓解AD的病理进程。Objective To investigate the neuroprotective potential of lycopene on inflammatory response and TLR4 pathway of choroid plexus in β-amyloid induced model of Alzheimer＇s disease. Methods Forty adult SD rats （body weight： （250±18.7）g were randomly divided into five groups （n=8）： control, AD model, AD＋lycopene （ig. 5mg/kg.d）, AD＋lycopene （ig. 10mg/kg.d） and lycopene group. The rats were adapted for one week prior to the treatmentsβ-amyloid （A[1.42） at dose of 8gg was administered bilaterally through intracerebroventricular （ICV） into hippocampus by using stereotaxic instrument in AD group and AD＋lycopene group rats. The control and lycopene groups were given an equal volume of saline. All rats were tested in a Morris water maze at weeks 2, 3, 4, 5 after the intervention to evaluate the learning and memory ability. Rats were then sacrificed and the blood samples were prepared for the quantification of TNF-ct, IL-I[3 and IL-6[3 by ELISA. The expressions of TLR4, NF-~B p65 mRNA and protein were detected by RT-qPCR and Western blot. Western blot was also usedto detect the expression of PS-1 and β-APP in hippocampus. Results Compared with the control group, the escape latency period and activity time in AD group were significantly longer （P〈0.05）. But the rats performed better in AD＋lycopene groups than in AD group （P〈 0.05）. Compared with the control group, the levels of TNF-a, IL-1β and IL-613 were significantly increased in AD group （P〈 0.05）, but significantly decreased in AD＋lycopene group （P〈 0.05）. Compared with the control group, the expressions of TLR4, NF-βB p65 mRNA and protein were also significantly increased in AD group （P〈 0.05）, but significantly decreased in AD＋lycopene groups （P〈 0.05）. Compared with the control group, the expressions of PS-1 and β-APP mRNA and protein in hippocampus were significantly increased in AD group （P〈 0.05）, but were reversed by lycopene treatment （P〈 0.05）. Conclusion Collective

关 键 词：番茄红素 脉络丛上皮 阿尔茨海默病 炎症反应 

分 类 号：R285.5[医药卫生—中药学]