低剂量苯并(a)芘慢性暴露对老年小鼠学习记忆能力的影响及机制  

Effects and its mechanism of chronic exposure to low dose benzoapyrene on learning and memory ability of aged mice

作　　者：方侃[1] 胡怀明[1] 姜华军[1] 艾志兵[2] 周圆[1] FANG Kan;HU Huai-ming;JIANG Hua-jun;AI Zhi-bing;ZHOU Yuan(Department of Pharmacy,Taihe Hospital Affiliated to Hubei University of Medicine,Shiyan Hubei,442000,China;Department of Neurology,Taihe Hospital Affiliated to Hubei University of Medicine,Shiyan Hubei,442000,China)

机构地区：[1]湖北医药学院附属太和医院药学部,湖北十堰442000 [2]湖北医药学院附属太和医院神经内科,湖北十堰442000

出　　处：《职业与健康》2021年第5期602-606,共5页Occupation and Health

基　　金：2019年十堰市科学技术研究与开发立项项目(19Y64)。

摘　　要：目的探讨低剂量苯并(a)芘(BaP)慢性暴露对老年小鼠学习记忆能力的影响及机制。方法选取健康雄性16月龄昆明小鼠100只,按照随机数字表法,将小鼠随机分为5组,空白对照组、溶剂对照组、BaP 0.1 mg/kg组、BaP 0.3 mg/kg组和BaP 0.6 mg/kg组,每组20只。每天定时灌胃,连续染毒120 d,染毒结束进行水迷宫测试和取材。用ELISA法检测各组小鼠海马组织超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)活性,丙二醛(MDA)、二羟环氧苯并芘-脱氧核糖核酸(BPDE-DNA)加合物及日淀粉样蛋白_(1~42)(Aβ_(1~42))的含量,用Western blot法检测Tau(pS396)、Tau(pT231)蛋白表达水平。结果与空白对照组比较,BaP 0.3、0.6 mg/kg组小鼠潜伏期明显延长、进入原平台象限的次数明显减少及在该象限的探索时间明显缩短,差异均有统计学意义(均P<0.05)。与空白对照组比较,BaP 0.3、0.6 mg/kg组小鼠SOD、GSH-Px活性明显降低、MDA含量明显升高,差异均有统计学意义(均P<0.05);与空白对照组比较,BaP 0.3、0.6 mg/kg组小鼠BPDE-DNA加合物及Aβ_(1~42)含量明显升高,差异均有统计学意义(均P<0.05);与空白对照组比较,BaP 0.3、0.6 mg/kg组小鼠海马组织P-Tau(pS396)、P-Tau(pT231)蛋白表达明显升高,差异均有统计学意义(均P<0.05)。而上述各指标在BaP 0.3 mg/kg组与BaP 0.6mg/kg组之间变化明显,差异均有统计学意义(均P<0.05)。结论低剂量BaP慢性暴露可引起老年小鼠的学习记忆能力明显下降,其机制可能与BaP诱发海马组织氧化应激和DNA损伤,并进一步上调Aβ_(1~42)、P-Tau(pS396)及P-Tau(pT231)蛋白的表达水平有关。Objective To investigate the effects and its mechanism of chronic exposure to low dose benzoapyrene(BaP)on learning and memory ability of aged mice.Methods Totally 100 healthy male kunming mice aged 16 months were selected and randomly divided into five groups according to the random number table method:blank control group,solvent control group,BaP 0.1 mg/kg group,BaP 0.3 mg/kg group and BaP 0.6 mg/kg group,20 in each group.Gavage was given regularly every day for 120 days.After poisoning,water maze test and sampling were performed.The activities of superoxide dismutase(SOD),glutathione peroxidase(GSH-Px),and the contents of malondialdehyde(MDA),BPDE-DNA adduct and amyloidβ-protein_(1-42)(Aβ_(1-42)) in the hippocampal tissues of mice were detected by ELISA.The expression levels of Tau(pS396) and Tau(pT231) were detected by Western blot.Results Compared with the blank control group,the incubation periods of mice in BaP 0.3 and 0.6 mg/kg groups was significantly prolonged,the frequency of entering the original platform quadrant was significantly reduced,and the exploration time in the quadrant was significantly shortened,and the differences were statistically significant(all P<0.05).Compared with the blank control group,the activities of SOD and GSH-Px in hippocampal tissues of mice in BaP 0.3 and 0.6 mg/kg groups were significantly decreased,while the contents of MDA were significantly increased,and the differences were statistically significant(all P<0.05).Compared with the blank control group,the contents of BPDE-DNA adducts and Aβ_(1-42) in BaP 0.3 and 0.6 mg/kg groups were significantly increased,and the differences were statistically significant(all P<0.05).Compared with the blank control group,the protein expressions of P-Tau(pS396)and P-Tau(pT231) in the hippocampus of mice in BaP 0.3 and 0.6 mg/kg groups were significantly increased,and the differences were statistically significant(all P<0.05).The above indexes changed significantly between the BaP0.3 mg/kg group and the BaP 0.6 mg/kg group,and the dif

关 键 词：苯并(A)芘 老年小鼠 学习记忆 氧化应激 β淀粉样蛋白_(1~42) 过度磷酸化Tau蛋白 

分 类 号：R114[医药卫生—卫生毒理学]