阿魏酸对三甲基氯化锡诱导大鼠学习记忆功能损伤的保护作用  

Protective effect of ferulic acid on trimethyltin chloride-induced learning and memory impairment in rats

作　　者：李国樑[1] 易沐诗 胡悦 吴幼仪 陆丰荣[1] 郑杰蔚 李和成 刘莉莉[1] LI Guoliang;YI Mushi;HU Yue;WU Youyi;LU Fenrong;ZHENG Jiewei;LI Hecheng;LIU Lili(Department of Toxicology,Guangdong Province Hospital for Occupational Disease Prevention and Treatment,Guangzhou,Guangdong 510300,China)

机构地区：[1]广东省职业病防治院毒理实验所,广东广州510300

出　　处：《中国职业医学》2024年第4期374-380,共7页China Occupational Medicine

基　　金：广东省医学科学技术研究基金(B2021017,A2022102);广东省中医药局科研项目(20212029,20221062);广东省职业病防治院科研重点项目(Z2023-06);广东省职业病防治院青年拔尖人才项目(Z2024-07)。

摘　　要：目的建立三甲基氯化锡(TMT)诱导的大鼠学习记忆功能损伤模型,探讨阿魏酸的保护作用及可能的作用机制。方法将无特定病原体级雄性SD大鼠随机分为对照组、TMT染毒组、氟西汀组和25、50、100 mg/kg阿魏酸组,后5组大鼠均一次性腹腔注射剂量为8 mg/kg体质量的TMT溶液,对照组注射等体积的0.9%氯化钠溶液。TMT注射24 h后,氟西汀组大鼠予剂量为10 mg/kg体质量的氟西汀,3个阿魏酸组大鼠分别予剂量为25、50、100 mg/kg体质量的阿魏酸,对照组和TMT染毒组大鼠均予等体积的0.9%氯化钠溶液,1次/d,连续灌胃28 d。采用Morris水迷宫实验和明暗箱穿梭实验测试大鼠的学习记忆能力,采用实时荧光定量聚合酶链式反应、蛋白质印迹法分别检测大鼠海马组织中核转录因子-κB(NF-κB)、肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)的mRNA和蛋白表达,采用酶联免疫吸附实验检测大鼠海马组织中活性氧自由基(ROS)、丙二醛的水平和超氧化物歧化酶(SOD)、过氧化氢酶(CAT)的活力。结果与对照组比较,TMT染毒组大鼠第4天的逃避潜伏期延长(P<0.05),穿越平台次数减少(P<0.05),目标象限停留时间和进入暗箱潜伏期均缩短(P值均<0.05);大鼠海马组织中NF-κB、TNF-α和IL-1β的mRNA和蛋白相对表达水平均上调(P值均<0.05),ROS和丙二醛水平均增加(P值均<0.05),SOD和CAT活力均降低(P值均<0.05)。除25 mg/kg阿魏酸组大鼠的逃避潜伏期和目标象限停留时间外,与TMT染毒组比较,3个阿魏酸组大鼠第4天的逃避潜伏期均降低(P值均<0.05),穿越平台次数均增加(P值均<0.05),目标象限停留时间和进入暗箱潜伏期均延长(P值均<0.05)。除50 mg/kg阿魏酸组大鼠的TNF-α蛋白相对表达水平外,与TMT染毒组比较,50和100 mg/kg阿魏酸组大鼠海马组织中NF-κB、TNF-α和IL-1β的mRNA和蛋白表达均下调(P值均<0.05),ROS和丙二醛水平均降低(P值均<0.05),SOD和CAT活力均升高(P值Objective To establish a trimethyltin chloride(TMT)-induced learning and memory impairment model in rats,and to investigate the protective effects and potential mechanisms of ferulic acid.Methods Specific pathogen-free male SD rats were randomly divided into control group,TMT intoxication group,fluoxetine group and 25,50,100 mg/kg ferulic acid group.The rats in the last five groups were injected with a dose of 8 mg/kg body weight TMT solution,and the rats in control group were injected with the same volume of 0.9%sodium chloride solution.After 24 hours of TMT injection,the rats in fluoxetine group were treated 10 mg/kg body weight of fluoxetine,the rats in the three ferulic acid groups were treated with ferulic acid at doses of 25,50,and 100 mg/kg body weight,respectively.The rats in the control group and TMT intoxication group were treated with the same volume of 0.9%sodium chloride solution,once per day for continuous gavage for 28 days.Morris water maze experiment and light-dark box test were used to assess the learning and memory abilities of the rats.The mRNA and protein expressions of nuclear transcription factor-κB(NF-κB),tumor necrosis factor-α(TNF-α)and interleukin-1β(IL-1β)in the rat hippocampus were detected by real-time quantitative polymerase chain reaction and Western blot.The levels of reactive oxygen species(ROS)and malondialdehyde(MDA)and the activities of superoxide dismutase(SOD)and catalase(CAT)in the rat hippocampus were detected by enzyme-linked immunosorbent assay.Results Compared with the control group,rats of TMT intoxication group on day four had prolonged escape latency(P<0.05),fewer platform crossing(P<0.05),shorter time spent in the target quadrant and shorter latency to enter the dark compartment(all P<0.05).The mRNA and protein relative expression of NF-κB,TNF-αand IL-1βincreased(all P<0.05),ROS and MDA levels increased(all P<0.05),SOD and CAT activities decreased(all P<0.05)in the rat hippocampus of TMT intoxication group on day four compared with that of the control group

关 键 词：三甲基氯化锡 阿魏酸 学习记忆功能 氧化应激 炎症反应 

分 类 号：R135.1[医药卫生—劳动卫生] R114[医药卫生—公共卫生与预防医学]