参麻益智方对血管性痴呆模型大鼠Nrf2/HO-1通路及小胶质细胞的影响  

Effects of Shenma Yizhi Prescription on Nrf2/HO-1 Pathway and Microglia in Rats with Vascular Dementia

作　　者：李琨 裴卉[2] 曹宇[2] 马丽娜[2] 李浩[2] LI Kun;PEI Hui;CAO Yu;MA Lina;LI Hao(Beijing Open University,Beijng 100081,China;Xiyuan Hospital of China Academy of Chinese Medical Sciences,Beijng 100091,China)

机构地区：[1]北京开放大学,北京100081 [2]中国中医科学院西苑医院,北京100091

出　　处：《中国中医药信息杂志》2020年第12期38-42,共5页Chinese Journal of Information on Traditional Chinese Medicine

基　　金：国家自然科学基金(81603616);北京市科委“十病十药”研发项目(Z171100001717016)。

摘　　要：目的观察参麻益智方对血管性痴呆(VaD)模型大鼠Nrf2/HO-1通路及小胶质细胞的影响,探讨其治疗VaD的分子机制。方法Wistar大鼠60只随机分为空白组、假手术组、模型组和参麻益智方低、中、高剂量组,各给药组给予相应剂量药物。大鼠采用微血栓栓塞法造模,给药4周后进行学习记忆能力测试,采用RT-qPCR和Western blot分别检测大鼠海马组织核因子E2相关因子2(Nrf2)、血红素加氧酶1(HO-1)基因和蛋白的表达,免疫组化检测小胶质细胞激活程度。结果与假手术组比较,模型组大鼠水迷宫实验逃避潜伏期均明显延长,海马组织Nrf2、HO-1蛋白和mRNA表达均明显升高,iba-1标记的小胶质细胞数量显著增多,标记程度增强,形态上胞体变圆,分支减少,差异有统计学意义(P<0.05,P<0.01);与模型组比较,参麻益智方中、高剂量组大鼠水迷宫实验逃避潜伏期均明显缩短,Nrf2蛋白和mRNA表达均明显升高,参麻益智方高剂量组大鼠HO-1 mRNA表达显著升高,参麻益智方中、高剂量组大鼠小胶质细胞被iba-1标记的程度减轻,数量减少,胞体变小,分支细长,差异有统计学意义(P<0.05,P<0.01)。结论参麻益智方可明显改善VaD大鼠模型学习记忆能力,其机制可能与参麻益智方促进Nrf2/HO-1通路蛋白及基因表达,以及抑制小胶质细胞过度激活而发挥抗炎、抗氧化应激作用相关。Objective To evaluate the effects of Shenma Yizhi Prescription on Nrf2/HO-1 pathway and microglia in rats with vascular dementia(VaD);To explore its molecular mechanism of VaD treatment.Methods Totally 60 Wistar rats were randomly divided into blank group,sham-operation group,model group,Shenma Yizhi Prescription low-,medium-,and high-dosage groups.Each administration group was given relevant dosage of medicine.Microthromboembolism was used to create the model.The learning and memory abilities of model rats were tested after 4 weeks of administration.RT-qPCR and Western blot were used to detect the expressions of Nrf2,HO-1 protein and gene in hippocampus of rats.Activation of microglia was detected by immunohistochemistry.Results Compared with the sham-operation group,the escape latency of the water maze experiment in the model group was significantly prolonged,the protein contents of Nrf2 and HO-1 increased,the mRNA expressions of Nrf2 and HO-1 increased,the number of microglia labeled by iba-1 significantly increased,the degree of labeling was enhanced,the cell body became round and the branches decreased,with statistical significance(P<0.05,P<0.01).Compared with the model group,the escape latency of the water maze experiment in Shenma Yizhi Prescription medium-and high-dosage groups was significantly shortened,the expression of protein and m RNA of Nrf2 significantly increased,the expression of HO-1 m RNA significantly increased in Shenma Yizhi Prescription high-dosage group,the degree of microglia labeled by iba-1 was reduced in Shenma Yizhi Prescription medium-and high-dosage groups,the number of microglia was decreased,the cell body was smaller,and the branches were slender,with statistical significance(P<0.01,P<0.05).Conclusion Shenma Yizhi Prescription can significantly improve the learning and memory abilities of VaD rats.The mechanism may be related to the anti-inflammatory and anti-oxidative stress effects of Shenma Yizhi Prescription on promoting Nrf2/HO-1 pathway protein and gene expression,and inhib

关 键 词：参麻益智方 血管性痴呆 核因子E2相关因子2 血红素加氧酶1 小胶质细胞 大鼠 

分 类 号：R285.5[医药卫生—中药学]