姜黄素对于老年痴呆症模型大鼠外周血单个核细胞中组织蛋白酶B表达的影响  

The effect of Curcumin on Cathepsin B expression in peripheral blood mononuclear cells derived from Alzheimer's disease model rats

作　　者：陈汉泽 李进伟[1] 师含 滕伟禹[1] 田力[2] CHEN Hanze;LI Jinwei;SHI Han(Deparment of Neurology,The First Affiliated Hospital of China Medical University,Shenyang 110001,China)

机构地区：[1]中国医科大学附属第一医院神经内科,辽宁沈阳110001 [2]中国医科大学附属盛京医院老年病科,辽宁沈阳110004

出　　处：《中风与神经疾病杂志》2018年第8期726-729,共4页Journal of Apoplexy and Nervous Diseases

基　　金：国家科技部十三五重大专项计划项目(No.2017ZX10201101);沈阳市科技项目(No.17-230-9-31; No.F16-206-9-03);盛京医院院内课题(No.ME63)

摘　　要：目的研究姜黄素对β淀粉样蛋白(Aβ1-42)诱导的老年痴呆(AD)大鼠外周血单个核细胞溶酶体中组织蛋白酶(Cat B)的表达及对Aβ的降解能力的作用;同时探讨对于大鼠认知功能的影响。方法将Aβ1-42微量注射至SD大鼠右侧海马制作AD模型大鼠,假手术组海马注入等量PBS。于建模后随机分为AD模型组及姜黄素干预组,姜黄素干预组给予300 mg/(kg·d)二甲基亚砜(DMSO)溶解的姜黄素连续腹腔注射7 d,AD模型组以及假手术组腹腔注射等量DMSO;术后第9天心脏穿刺采集大鼠外周血,并采用Ficoll密度梯度离心法分离外周血单个核细胞,用定量PCR方法及酶活性分析法检测其中Cat B表达;采用定位航行和空间探索水迷宫试验分别检测大鼠的学习和记忆能力。结果与假手术组及AD模型组相比较,经姜黄素处理过的干预组大鼠外周血单个核细胞中Cat B表达及活性均上调;且经姜黄素干预后AD模型大鼠空间学习记忆能力明显改善(P=0. 021)。结论姜黄素可以上调AD模型大鼠外周血单个核细胞Cat B表达及活性;姜黄素有改善Aβ1-42诱导的AD模型大鼠空间学习记忆障碍的作用。Objective To study the role and significance of curcumin on Cathepsin B(Cat B)levels in peripheral blood mononuclear cells(PBMC),derived from rats after micro-injected into the right hippocampus with Aβ1-42,and to investigate the effect of curcumin on cognitive impairment of the Alzheimer’s disease(AD)model rats.Methods Adult male Wistar rats were mounted in a stereotaxic apparatus and received injection of 10μl aggregated Aβ1-42 or PBS into hippocampus(PBS as sham group).Then the rats were divided into three groups:sham group,model group and curcumin administrated group.Curcumin dissolved with DMSO[300 mg/(kg·d)]was administrated by intraperitoneal injection to the AD model group for 7 d.At 9 d,heparinized whole blood was freshly drawn from rat heart,separated PBMCs with ficoll density gradient centrifugation.Cat B levels in PBMCs were analyzed by real-time quantitative PCR(RT-qPCR)and activity assay.Meanwhile Morris water maze(MWM)was used to study the learning and memory ability in each group every day.Results Cat B levels were increased in PBMC from the curcumin administrated group compared to sham group and model group,which contributed to degeneration to Aβ.MWM test showed the rats in curcumin administrated group had shorter escape latencies compared with those in model group(P=0.021).Conclusion Curcumin could up-regulate the expression of Cat B in PBMC,and involved partly in improving the spatial learning and memory dysfunction of AD rats.

关 键 词：AD模型 姜黄素 外周血单个核细胞 Β淀粉样蛋白 组织蛋白酶 

分 类 号：R749.1[医药卫生—神经病学与精神病学]