灯盏乙素通过细胞转运途径对阿尔茨海默病大鼠β-淀粉样蛋白跨血脑屏障的影响  

Effect of Breviscapine onβ-amyloid across Blood-brain Barrier of Alzheimer′s Disease Rats Via Cellular Transporter Pathway

作　　者：李可 苗果 柳秋 赵昆朋 LI Ke;MIAO Guo;LIU Qiu;ZHAO Kunpeng(Nanshi Hospital of Nanyang,Nanyang 473000,Henan,China)

机构地区：[1]南阳南石医院,河南南阳473000 [2]新乡医学院第二附属医院

出　　处：《中西医结合心脑血管病杂志》2024年第10期1782-1786,共5页Chinese Journal of Integrative Medicine on Cardio-Cerebrovascular Disease

基　　金：2019年河南省医学科技攻关计划项目(No.LHGJ20190478)。

摘　　要：目的:探讨灯盏乙素对阿尔茨海默病(AD)大鼠β-淀粉样蛋白(Aβ)跨血脑屏障(BBB)的影响及其机制。方法:无特定病原体(SPF)级SD大鼠70只,随机分为假手术组、模型组、灯盏乙素低剂量组、灯盏乙素高剂量组以及阳性对照组,除假手术组大鼠外,其余组大鼠侧脑室注射Aβ_(1-42)氯化钠溶液建立AD大鼠模型,灯盏乙素低剂量和高剂量组大鼠分别灌胃灯盏乙素5 mg/kg和10 mg/kg,阳性对照组灌胃盐酸多奈哌齐0.9 mg/kg,持续30 d,观察大鼠行为能力以及血脑屏障通透性,进行苏木精-伊红(HE)染色和免疫组化染色,蛋白质免疫印迹法(Western Blot)检测基质金属蛋白酶-9(MMP-9)、闭合蛋白-5(Claudin-5)、咬合蛋白(Occludin)、低密度脂蛋白相关蛋白(LRP-1)以及p糖蛋白(P-gp)表达情况。结果:模型组神经元细胞排列疏松、紊乱,细胞数量减少,可见明显空泡化,灯盏乙素低剂量组、灯盏乙素高剂量组及阳性对照组神经元细胞数量增多,空泡化细胞减少,细胞排列稍整齐致密。灯盏乙素低剂量组、灯盏乙素高剂量组及阳性对照组大鼠逃避潜伏期、伊文思蓝含量、Aβ斑块面积以及MMP-9蛋白相对表达量均低于模型组,穿过平台的次数以及LRP-1、P-gp、Claudin-5、Occludin蛋白相对表达量高于模型组(P<0.05)。结论:灯盏乙素可减轻AD大鼠神经元病理损伤,保护血脑屏障。Objective:To investigate the effect of breviscapine onβ-amyloid(Aβ)across blood-brain barrier(BBB)in rats with Alzheimer′s disease(AD)rats and its mechanism.Methods:Seventy specific pathogen free(SPF)SD rats were randomly divided into sham operation group,model group,scutellarin low-dose group,scutellarin high-dose group and positive control group.Except for sham operation group,the AD rat model was established by injecting Aβ1-42 sodium chloride solution into the lateral ventricle of the other groups.Scutellarin low-dose group and scutellarin high-dose group were gavaged scutellarin with 5 mg/kg and 10 mg/kg for 30 days respectively,and positive control group was gavaged donepezil hydrochloride with 0.9 mg/kg for 30 days.The behavioral ability and BBB permeability of rats were observed,and hematoxylin-eosin staining(HE)and immunohistochemical staining were performed.Matrix metalloproteinase-9(MMP-9),closure protein-5(Claudin-5),Occludin,low density lipoprotein-related protein(LRP-1)and P-glycoprotein(P-gp)were detected by Western Blot.Results:In the model group,the neuronal cells arranged loosely and disorganized,the number of cells reduced,and the vacuolation was obvious.The number of neuronal cells increased in the scutellarin low-dose group,scutellarin high-dose group and positive control group,and the number of vacuolated cells reduced,and the arrangement of the cells was slightly neat and dense.The escape latency,Evans blue content,Aβplaque area and relative expression of MMP-9 protein in the scutellarin low-dose group,scutellarin high-dose group and positive control group were lower than those in model group.The frequency of crossing the platform,the relative expression of LRP-1,P-gp,Claudin-5 and Occludin were higher than those in the model group(P<0.05).Conclusion:Breviscapine could alleviate pathological damage of neurons and protect BBB in rats with AD.

关 键 词：阿尔茨海默病 血脑屏障 Β-淀粉样蛋白 灯盏乙素 实验研究 

分 类 号：R285.5[医药卫生—中药学]