百草枯通过Wnt/β-catenin信号通路调控Aβ产生导致大鼠阿尔茨海默病样病变  

Paraquat causes Alzheimer's-like pathology in rats through Wnt/β-catenin signaling-mediated Aβproduction

作　　者：刘涛[1] 沈涛 李艳萍[2] 罗洪文[3] 张伟[1] LIU Tao;SHEN Tao;LI Yanping;LUO Hongwen;ZHANG Wei(Department of Emergency Medicine,Affiliated Hospital of Yunnan University,Kunming 650021,Yunnan,China;Department of Emergency Medicine,Diannan Central Hospital of Honghe/Gejiu People's Hospital,Honghe 661000,Yunnan,China;Outpatient Department,Xishuangbanna People's Hospital,Xishuangbanna 666100,Yunnan,China)

机构地区：[1]云南大学附属医院急诊医学部,云南昆明650021 [2]红河州滇南中心医院/个旧市人民医院急诊医学部,云南红河661000 [3]西双版纳州人民医院门诊部,云南西双版纳6661001

出　　处：《中国现代医生》2023年第35期68-71,共4页China Modern Doctor

基　　金：云南省科技厅-昆明医科大学应用基础研究联合专项资金项目面上项目(202001AY070001-093)。

摘　　要：目的阿尔茨海默病在中国的年发病率逐年升高,早期大量使用的除草剂百草枯可能是诱发阿尔茨海默病的因素,本研究通过构建百草枯中毒动物模型,分析其诱发阿尔茨海默病的机制。方法给SD大鼠灌喂百草枯,观察其行为,通过伊文思蓝染色观察血脑屏障的完整性,使用免疫印迹法检测脑组织中Aβ42的表达水平,同时使用ELISA检测炎症因子白细胞介素-1β、肿瘤坏死因子-α和诱导型一氧化氮合酶的表达水平。结果百草枯能显著增加脑组织中Aβ42的表达水平,同时破坏血-脑脊液屏障的完整性,增加血-脑脊液屏障中糖原合酶激酶-3β(glycogen synthase kinase-3β,GSK-3β)的表达水平。使用GSK-3β抑制剂能显著缓解百草枯导致的血-脑脊液屏障损伤和Aβ42的水平。结论百草枯可以通过上调GSK3β破坏血-脑脊液屏障的完整性,从而进入脑内,使Aβ42的表达水平升高。Objective The annual incidence of Alzheimer's disease in China is increasing year by year.The herbicide paraquat widely used in early China may be the factor inducing Alzheimer's disease.This study intends to analyze the mechanism of inducing Alzheimer's disease by constructing an animal model of paraquat poisoning.Methods SD rats were fed paraquat,and the integrity of blood-brain barrier was observed by Evans blue staining.The expression level of Aβ42 in brain tissue was detected by Western-blot,and the expression levels of inflammatory cytokines interleukin-1β,tumor necrosis factor-αand inducible isoform of nitric oxide synthase were detected by ELISA.Results Paraquat could significantly increase the expression level of Aβ42 in brain tissue,destroy the integrity of blood-brain barrier,and increase the expression level of GSK-3βin blood-brain barrier.Further results showed that the use of GSK-3βinhibitors significantly alleviated paraquat induced blood-brain barrier damage and Aβ42 levels.Conclusion Paraquat can damage the integrity of the blood-brain barrier by up-regulating GSK-3β,and eventually lead to paraquat entering the brain,which increases the expression level of Aβ42.

关 键 词：百草枯 阿尔茨海默病 血-脑脊液屏障 AΒ42 

分 类 号：R365[医药卫生—病理学]