地黄饮子调控PERK/eIF2α通路改善阿尔茨海默病小鼠脑内炎症微环境  

Dihuang Yinzi Regulating PERK/eIF2αPathway to Improve Inflammatory Microenvironment in Brain of Mice with Alzheimer′s Disease

作　　者：郭昕鑫 GUO Xinxin(The Affiliated Cancer Hospital to Harbin Medical University,Harbin Heilongjiang China 150000)

机构地区：[1]哈尔滨医科大学附属肿瘤医院,黑龙江哈尔滨150000

出　　处：《中医学报》2022年第9期1941-1946,共6页Acta Chinese Medicine

基　　金：黑龙江省科技攻关计划项目(ZHY19-W0413)。

摘　　要：目的:基于蛋白激酶R样内质网激酶(protein kinase R-like endoplasmic reticulum kinase,PERK)/真核细胞起始因子2α(eukaryotic initiation factor 2α,eIF2α)通路探讨地黄饮子对阿尔茨海默病(Alzheimer′s disease,AD)小鼠脑内炎症微环境的改善作用及其机制。方法:40只SPF级雄性APP/PS1双转基因小鼠随机分为空白对照组、模型组、多奈哌齐组(1 mg·kg^(-1))和地黄饮子组(0.25 g·kg^(-1)),每组各10只。除空白对照组外,其余组腹腔注射100 mg·kg^(-1)3-硝基丙酸建立AD模型。造模完成后,各组小鼠分别灌胃给予相应药物进行干预,空白对照组和模型组灌胃给予等体积生理盐水,每日1次,持续7 d。Morris水迷宫实验评价小鼠的学习记忆能力;ELISA法检测小鼠脑脊液中巨噬细胞炎性蛋白-2(macrophage inflammatory protein-2,MIP-2)、白细胞介素-1β(interleukin-1β,IL-1β)、肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)的水平;Western Blot法检测PERK/eIF2α通路相关蛋白表达水平。结果:与空白对照组比较,模型组穿越平台次数显著减少(P<0.05),目标象限停留时间显著缩短(P<0.05),相对象限停留时间及第2~5天逃避潜伏期显著延长(P<0.05),MIP-2、IL-1β、TNF-α、PERK/p-PERK、eIF2α/p-eIF2α及β-分泌酶1(β-secretase,BACE1)水平明显升高(P<0.05);与模型组比较,多奈哌齐组和地黄饮子组穿越平台次数显著增多(P<0.05),目标象限停留时间显著延长(P<0.05),相对象限停留时间及第2~5天逃避潜伏期显著缩短(P<0.05),MIP-2、IL-1β、TNF-α、PERK/p-PERK、eIF2α/p-eIF2α及BACE1水平明显降低(P<0.05)。结论:地黄饮子能显著改善AD小鼠学习记忆能力及脑内炎症微环境,其作用可能与抑制PERK/eIF2α信号通路的激活有关。Objective:Based on the PERK/eIF2αpathway,to explore the improvement effect and mechanism of Dihuang Yinzi on the inflammatory microenvironment in the brain of Alzheimer′s disease mice.Methods:40 SPF male APP/PS1 double transgenic mice were randomly divided into blank control group,model group,donepezil(1 mg·kg^(-1))group and Dihuang Yinzi(0.25 g·kg^(-1))group.10.Except for the blank control group,AD models were established by intraperitoneal injection of 100 mg·kg^(-1)3-nitropropionic acid.After the modeling was completed,the mice in each group were given corresponding drugs by gavage respectively for intervention,and the blank control group and the model group were given an equal volume of normal saline by gavage,once a day,for 7 days.Morris water maze test was used to evaluate the learning and memory ability of mice;ELISA was used to detect macrophage inflammatory protein-2(MIP-2),interleukin-1β(IL-1β)in the cerebrospinal fluid of mice,tumor necrosis factor-α(TNF-α)levels;Western Blot assay to detect protein kinase R-like endoplasmic reticulum kinase(PERK)/eukaryotic Expression levels of proteins related to eIF2αpathway.Results:Compared with the blank control group,the number of crossing platforms in the model group was significantly reduced(P<0.05),the residence time in the target quadrant was significantly shortened(P<0.05),and the limit residence time and escape latency on days 2-5 were significantly prolonged(P<0.05),the levels of MIP-2,IL-1β,TNF-α,PERK/p-PERK,eIF2α/p-eIF2αand BACE1 were significantly increased(P<0.05);compared with the model group,the donepezil group and the Dihuang Yinzi group,the number of crossing platforms was significantly increased(P<0.05),the stay time in the target quadrant was significantly prolonged(P<0.05),and the duration of stay in the target quadrant and the 2-5 day escape latency were significantly shortened(P<0.05),and the MIP-2,IL-1β,TNF-α,PERK/p-PERK,eIF2α/p-eIF2αand BACE1 levels were significantly decreased(P<0.05).Conclusion:Dihuang Yinzi can signific

关 键 词：地黄饮子 阿尔茨海默病 PERK/eIF2α通路 脑内炎症微环境 小鼠 

分 类 号：R285.5[医药卫生—中药学]