PGC-1α介导的线粒体生物发生在铝致小鼠学习记忆能力损伤中的作用研究  

Role of PGC-1α-mediated mitochondrial biogenesis in aluminum-induced learning and memory impairment in mice

作　　者：贺小玉 向长鑫 王茹[1] 刘洋[1] 殷金珠 张慧芳[1] HE Xiaoyu;XIANG Changxin;WANG Ru;LIU Yang;YIN Jinzhu;ZHANG Huifang(School of Public Health,Shanxi Medical University,Taiyuan Shanxi,030001,China;National Medicine Tongmei General Hospital,Datong Shanxi,037000,China)

机构地区：[1]山西医科大学公共与卫生学院,山西太原030001 [2]国药同煤总医院,山西大同037000

出　　处：《职业与健康》2024年第8期1013-1019,共7页Occupation and Health

基　　金：山西省自然科学基金(202203021211245);山西省神经疾病防治委级重点实验室(2020SY20)。

摘　　要：目的 探究海马过氧化物酶增殖体激活受体共激活因子-1α(peroxisome proliferator-activated receptor gamma coactivator-1α,PGC-1α)介导的线粒体生物发生在铝致小鼠学习记忆能力损伤中的作用。方法 将成年雄性SPF级ICR小鼠随机分为4组:对照组(生理盐水组)、铝剂量组[14、28和56μmol/kg Al(mal)3],染毒3个月。采用新物体识别实验检测小鼠学习及记忆能力的变化情况;采用透射电子显微镜观察海马神经元细胞内线粒体结构的变化;采用比色法检测小鼠海马三磷酸腺苷(adenosine triphosphate,ATP)的含量;采用反转录-聚合酶链反应(reverse transcription-polymerase chain reaction,RT-PCR)检测海马PGC-1α、核呼吸因子1(nuclear respiratory factor 1,NRF-1)、线粒体转录因子A(mitochondrial transcription factor A,TFAM)的mRNA含量和线粒体DNA(mitochondrial DNA,mtDNA)的含量;Western blotting检测海马PGC-1α、TFAM和NRF-1等的蛋白表达。结果 新物体识别实验结果显示,随着染铝剂量的增加,各组小鼠偏好指数、辨别指数逐渐下降(F=5.857、13.849,均P<0.05)。透射电镜结果显示,对照组线粒体结构完整、外膜和嵴清晰可见,染铝组线粒体呈现空泡样改变,正常的线粒体结构消失。随着染铝剂量的增加,小鼠海马mtDNA含量、ATP含量逐渐降低(F=313.923、89.887,均P<0.05)。与对照组(1.00±0.00)相比,染铝组海马PGC-1α、NRF-1和TFAM mRNA的表达量均出现下降的趋势,56μmol/kg Al(mal)3组PGC-1α、NRF-1、TFAM mRNA水平显著降低为0.53±0.08、0.21±0.08、0.42±0.06(P<0.05)。与对照组(1.00±0.00)相比,染铝组海马PGC-1α、NRF-1和TFAM的蛋白表达量均出现下降的趋势,56μmol/kg Al(mal)3组海马PGC-1α、NRF-1和TFAM的蛋白表达显著降低至0.66±0.15、0.50±0.22、0.60±0.77(P<0.05),呈现一定的剂量反应关系。结论 铝可致小鼠海马组织内线粒体生物发生相关信号通路PGC-1α-NRF-1-TFAM抑制,使神经元mt DNA数量下降而抑制细胞内Objective To explore the role of peroxisome proliferator-activated receptor gamma coactivator-1α(PGC-1α)-mediated mitochondrial biogenesis in aluminum-induced learning and memory impairment in mice.Methods The adult male SPF ICR mice were randomly divided into four groups:control group(saline group),aluminum exposure groups[14,28,56 μmol/kg Al(mal)3],which were exposed for three months.The new object recognition experiment was used to detect the changes of learning and memory ability of mice.The changes of mitochondrial structure in hippocampal neurons were observed by transmission electron microscope.The content of adenosine triphosphate(ATP) in hippocampus of mice was detected by corresponding kit.The m RNA contents of PGC-1α,nuclear respiratory factor 1(NRF-1) and mitochondrial transcription factor A(TFAM) and mitochondrial DNA(mtDNA) contents were detected by reverse transcription-polymerase chain reaction(RT-PCR).The Western blotting was used to detect the expression of PGC-1α,TFAM and NRF-1 in hippocampus.Results The experimental results of new object recognition showed that the preference index and discrimination index of mice in each group decreased gradually with the increase of aluminum exposure dose(F=5.857,13.849,both P<0.05).The results of transmission electron microscope showed that the structure of mitochondria in the control group was complete,the outer membrane and crista were clearly visible,and the mitochondria in the aluminum exposed groups showed vacuolar changes,and the normal mitochondrial structure disappeared.The contents of mt DNA and ATP in hippocampus of mice decreased gradually with the increase of aluminum exposure dose(F=313.923,89.887,both P<0.05).Compared with the control group(1.00±0.00),the expressions of PGC-1α,NRF-1 and TFAM mRNA in hippocampal neurons in aluminum exposure groups all showed a downward trend,and the levels of PGC-1α,NRF-1 and TFAM m RNA in 56 μmol/kg Al(mal)3group were significantly reduced to 0.53±0.08,0.21±0.08,0.42±0.06(P<0.05).Compared with the

关 键 词：铝 线粒体生物发生 过氧化物酶增殖体激活受体共激活因子-1α 核呼吸因子1 线粒体转录因子A 学习记忆 

分 类 号：R-332[医药卫生]