IGF2/JAK2/STAT3通路在麦芽酚铝致大鼠学习记忆损伤的作用  

Effects of IGF2/JAK2/STAT3 pathway on learning and memory impairment induced by aluminummaltol in rats

作　　者：贾婧静 胡倩 贺婵婷 牛侨[1] JIA Jing-jing;HU Qian;HE Chan-ting;NIU Qiao(School of Public Health,Shanxi Medical University,Taiyuan,Shanxi 030001,China)

机构地区：[1]山西医科大学公共卫生学院,山西太原030001 [2]山西医科大学基础医学院

出　　处：《现代预防医学》2024年第10期1865-1871,共7页Modern Preventive Medicine

基　　金：山西省基础研究计划(20210302124582);国家自然科学基金面上项目(82204003、82173492)。

摘　　要：目的探讨IGF2/JAK2/STAT3通路在麦芽酚铝致大鼠学习记忆损害中的作用机制。方法将32只SD大鼠随机分为生理盐水对照组和低、中、高麦芽酚铝染毒组(10、20和40μmol/kg)四组,腹腔注射,隔天染毒,连续三个月。染毒结束后,采用Morris水迷宫检测大鼠学习记忆能力,HE染色检测大鼠海马神经元形态。采用实时荧光定量PCR检测海马组织中IGF2 mRNA水平,Western Blotting检测海马组织中Cleaved Caspase3、IGF2、p-JAK2(Tyr1007/1008)、p-STAT3(Ser727)蛋白的相对表达水平。结果随着染铝剂量的升高,各组大鼠同一天逃避潜伏期逐渐延长,目标象限停留时间和穿越平台次数都逐渐减少(F=7.900,P=0.001;F=6.693,P=0.002)。HE染色结果显示,随着染铝剂量的升高海马组织CA1区神经元个数逐渐下降且排列明显松散(F=25.947,P<0.001)。随着染铝剂量增高,凋亡相关蛋白Bcl-2水平逐渐下降(F=83.235,P<0.001),Bax(F=153.189,P<0.001)和Cleaved Caspase3(F=11.636,P<0.01)蛋白的相对表达量逐渐增高,IGF2 mRNA和IGF2、p-JAK2(Tyr1007/1008)、p-STAT3(Ser727)蛋白相对表达量均逐渐减少(F=18.423,P<0.001;F=11.072,P=0.001;F=55.161,P<0.001;F=10.481,P=0.001)。结论麦芽酚铝通过抑制IGF2/JAK2/STAT3通路引起细胞凋亡从而损伤大鼠的学习记忆能力。Objective To investigate the mechanism of IGF2/JAK2/STAT3 on learning and memory impairment induced by aluminum maltol in rats.Methods A total of 32 SD rats were divided into normal saline control group and low,medium and high maltol aluminum exposure groups(10,20 and 40μmol/kg)by random number table,respectively,and intraperitoneally injected every other day for three months.After exposure,Morris water maze was applied to examine the learning and memory ability of rats,and HE staining was used to check the arrangement of hippocampal neurons.Real-time fluorescence quantitative PCR was applied to detect the relative expression level of IGF2 mRNA in hippocampus of rats.Western Blotting was used for detecting the relative protein expression levels of Cleaved Caspase3,IGF2,p-JAK2(Tyr1007/1008),and p-STAT3(Ser727)in the hippocampus of rats.Results With the increase of aluminum dose,the escape latency of rats in the same day was prolonged,and the residence time in the target quadrant and the times of crossing the platform were gradually reduced(F=7.900,P=0.001;F=6.693,P=0.002).HE staining results showed that the number of neurons in CA1 region of hippocampus gradually decreased and the arrangement of neurons was obviously loose with the increase of aluminum dose(F=25.947,P<0.001).With increasing aluminum dose,apoptosis-associated protein Bcl-2 levels decreased gradually(F=83.235,P<0.001),Bax(F=153.189,P<0.001)and Cleaved Caspase3(F=11.636,P<0.01)levels was gradually increased,and the relative expression levels of IGF2 mRNA and IGF2,p-JAK2(Tyr1007/1008),p-STAT3(Ser727)proteins decreased gradually with the increase of aluminum dose(F=18.423,P<0.001;F=11.072,P=0.001;F=55.161,P<0.001;F=10.481,P=0.001).Conclusion Aluminum maltol can induce cell apoptosis by inhibiting IGF2/JAK2/STAT3 pathway,which could damage the learning and memory ability of rats.

关 键 词：麦芽酚铝 细胞凋亡 IGF2/JAK2/STAT3 学习记忆能力 

分 类 号：R114[医药卫生—卫生毒理学]