miR-103a-3p/RCAN1通路在铝致大鼠学习记忆损害的作用  

Effect of miR-103a-3p/RCAN1 pathway on learning and memory impairment induced by aluminum in rats

作　　者：徐旭 宋珊珊 肖雯洁 雷敏敏 宋静[1] 杨晓娟[1,2] XU Xu;SONG Shan-shan;XIAO Wen-jie;LEI Min-min;SONG Jing;YANG Xiao-juan(Department of Labor Health,School of Public Health,Shanxi Medical University,Taiyuan,Shanxi 030001,China;不详)

机构地区：[1]山西医科大学公共卫生学院劳动卫生教研室,山西太原030001 [2]山西医科大学第一医院老年科,山西太原030001

出　　处：《现代预防医学》2023年第21期3969-3973,共5页Modern Preventive Medicine

基　　金：山西省留学人员科技活动择优资助项目(20200008);山西省基础研究计划(202103021224398)。

摘　　要：目的 探究miR-103a-3p/钙调磷酸酶调节因子1(Regulator of calcineurin 1, RCAN1)通路在麦芽酚铝致大鼠记忆损伤中的作用。方法 将32只雄性SD大鼠按体重随机分为对照组(0μmol/kg)、低剂量染铝组(10μmol/kg)、中剂量染铝组(20μmol/kg)和高剂量染铝组(40μmol/kg),每组各8只,对照组大鼠腹腔注射0.9%的生理盐水,染铝剂量组腹腔注射相应浓度的麦芽酚铝溶液,隔天染毒,持续3个月。染毒结束后用水迷宫实验检测大鼠的学习记忆能力;实时荧光定量PCR法检测miR-103a-3p和RCAN1基因表达;Western blotting检测大鼠海马中RCAN1,糖原合成激酶-3β(GSK-3β)和磷酸化tau蛋白的相对表达量。结果 染铝组大鼠前5 d逃避潜伏期均高于对照组,在第6 d空间探索期,染铝组在目标象限停留时间以及穿过平台的次数均低于对照组(P<0.05);与对照组相比,染铝组大鼠海马miR-103a-3p基因表达水平下降(P<0.001),而RCAN1基因表达水平升高(P<0.001);与对照组相比,染铝组大鼠海马RCAN1, GSK3β,p-tau(ser396)蛋白表达升高(P<0.001)。结论 miR-103a-3p/RCAN1通路参与调节铝致学习记忆损害。Objective To explore the role of miR-103a-3p/regulator of calcineurin1(RCAN1)pathway in maltol aluminum induced memory impairment in rats.Methods In total 32 male SD rats were randomly divided into control group(0μmol/kg),low dose aluminum exposure group(10μmol/kg),medium dose aluminum exposure group(20μmol/kg),and high dose aluminum exposure group(40μmol/kg),with 8 rats in each group.The rats in the control group were intraperitoneally injected with 0.9%normal saline,and the aluminum group was injected with maltol aluminum solution of corresponding concentration every other day for 3 months.After exposure,the learning and memory ability of rats was assessed by water maze test,the gene expression of miR-103a-3p and RCAN1 was detected by real-time fluorescence quantitative PCR,and the relative expressions of RCAN1,glycogen synthesis kinase-3β(GSK-3β),and phosphorylated tau protein in hippocampus were detected by Western blotting.Results The escape latency in the aluminum exposed group was higher than that in the control group in the first five days,and the residence time in the target quadrant and the number of times crossing the platform in the aluminum exposed group were lower than those in the control group(P<0.05)on the sixth day of spatial exploration.Compared with the control group,the expression level of miR103a-3p gene in hippocampus of aluminum exposed group decreased(P<0.001),while the expression level of RCAN1 gene increased(P<0.001).Compared with the control group,the expression of RCAN1,GSK3β,and p-tau(ser396)protein in hippocampus of aluminum exposed group increased(P<0.001).Conclusion MiR-103a-3p/RCAN1 pathway is involved in the regulation of learning and memory impairment induced by aluminum.

关 键 词：铝 miR-103a-3p 钙调磷酸酶调节因子1 TAU蛋白磷酸化 学习记忆 

分 类 号：R114[医药卫生—卫生毒理学]