刘仙红,陈丹,曾晓晓,董阳婷,邓婕,齐晓岚,吴昌学,李毅,宋辉,官志忠
LIU Xianhong,CHEN Dan,ZENG Xiaoxiao,DONG Yangting,DENG Jie,QI Xiaolan,WU Changxue,LI Yi,SONG Hui,GUAN Zhizhong

• 1:贵州医科大学地方病与少数民族性疾病教育部重点实验室
• 2:贵州医科大学贵州省医学分子生物学重点实验室
• 3:贵州医科大学分子生物学重点实验室
• 4:贵州医科大学附院病理科

摘要(Abstract)：

目的:研究慢性氟中毒大鼠脑组织中过氧化物酶体增殖激活受体γ辅激活因子(PGC-1α)水平,探讨PGC-1α与学习记忆能力的关系。方法:SD大鼠60只,随机分为对照组(饮水含氟量<0. 5 mg/L)、低氟组(饮水含氟量为5. 0 mg/L)、高氟组(饮水含氟量为50. 0 mg/L),染氟时间分别为3个月及6个月;分别于染氟3月及6月时,用Morris水迷宫测定大鼠学习记忆能力,采用氟离子选择电极法测定大鼠血清氟含量,用蛋白印记方法检测大鼠海马及皮质组织中PGC-1α蛋白表达水平,分析大鼠海马及皮质PGC-1α蛋白水平与血清氟含量及空间学习记忆能力的相关性。结果:染氟大鼠逃避潜伏期较对照组显著延长、穿越平台次数及逗留平台象限时间明显缩短,以染氟6月组大鼠更明显(P <0. 05);血清氟含量随着染氟浓度的增高及染氟时间的延长而升高,高氟组大鼠血氟含量显著高于对照组,以染氟6月组大鼠尤为明显(P <0. 05);染氟大鼠海马区和皮质区的PGC-1α蛋白表达水平随着染氟浓度的增加和染氟时间的延长而逐渐下降,染氟6月组大鼠海马及皮质PGC-1α蛋白与血氟含量呈负相关(r=-0. 574、-0. 516,P <0. 05)、与大鼠逗留平台象限时间呈正相关(r=0. 76、0. 60,P <0. 05)、与逃避潜伏期呈负相关(r=-0. 542、-0. 58,P <0. 05)。结论:慢性氟中毒大鼠大脑组织PGC-1α蛋白表达水平降低,可能是氟中毒大鼠空间学习记忆能力降低的机制之一。
Objective: To investigate the changes of peroxisome proliferators-activated receptor γ coactivator(PGC-1α) in the brain of rats with chronic fluorosis and to explore the role of PGC-1α in the pathogenesis of chronic fluorosis and its relationship with learning and memory. Methods: 60 Sprague Dawley(SD) rats were divided randomly into control group(fluoride content of drinking water< 0. 5 mg/L),low fluoride group(fluoride content of drinking water is 5. 0 mg/L). L),high fluoride group(fluoride content of drinking water is 50. 0 mg/L),treatd for 3 and 6 months. The learning and memory ability were determined by Morris water maze test in 3 and 6 months; the fluoride content in serum was detected by Fluoride-ion selective electrode; the protein expression level of PGC-1α in brain tissue was detected by Western blotting; the correlation between PGC-1α protein expression and serum fluoride content and spatial learning and memory indices were also analyzed. Result: The escape latency of rats was significantly longer than that of the control group,the total number of space explorations was significantly reduced,and the time of the quadrant stayed platform was shortened significantly in rats treated for 6 months(P < 0. 05). The blood fluoride content increased with the increase of fluoride concentration and the time of fluoride exposure,and its content in the high fluoride group was significantly higher than that in the control group,especially in the 6-month fluorine-exposure group(P <0. 05). The expression of PGC-1α protein in the hippocampus and cortex of rats treated with fluorine were gradually decreased with the increase of the fluoride concentration and the time of fluoride exposure. The results of correlation analysis showed that there was a negative correlation between PGC-1αprotein in rats brain and blood fluoride content(r =-0. 574,-0. 516,P < 0. 05),and a positive correlation between the expression of PGC-1α protein in rats and resting platform quadrant(r = 0. 76,0. 60,P < 0. 05) and escape latency was negatively correlated(r =-0. 542,-0. 58,P < 0. 05).Conclusion: The decreased expression of PGC-1α protein in brain tissue may be one of the factors influencing the spatial learning and memory ability with chronic fluorosis.

关键词(KeyWords)： 氟中毒;过氧化物酶体增殖激活受体γ辅激活因子;学习记忆能力;脑组织;大鼠,Sprague-Dawley
fluorosis;peroxisome proliferator-activated receptor γ coactivator;learning and memory ability;brain tissue;rats,Sprague-Dawley

Abstract:

Keywords:

基金项目(Foundation): 国家自然科学基金资助项目(81760571);; 贵州省创新计划资助项目[黔教合协同创新中心(2014)06,黔科通(2016)161];; 贵阳市联合基金资助项目[筑科合同(2017)30-3号]

作者(Author): 刘仙红,陈丹,曾晓晓,董阳婷,邓婕,齐晓岚,吴昌学,李毅,宋辉,官志忠
LIU Xianhong,CHEN Dan,ZENG Xiaoxiao,DONG Yangting,DENG Jie,QI Xiaolan,WU Changxue,LI Yi,SONG Hui,GUAN Zhizhong

DOI: 10.19367/j.cnki.1000-2707.2018.10.007

参考文献(References)：

• [1]魏露莎,禹文峰,詹赞琳,等.凋亡诱导因子在慢性氟中毒大鼠脑组织神经细胞凋亡中的作用[J].中华地方病学杂志,2015,34(9):655-659.
• [2]魏娜,董阳婷,王娅,等.慢性氟中毒对大鼠仔代神经系统发育的影响及维生素E的拮抗作用[J].中华地方病学杂志,2014,33(2):125-128.
• [3]GUBELLINI P,PICCONI B,DI FILIPPO M,et al.Downstream mechanisms triggered by mitochondrial dysfunction in the basal ganglia:From experimental models to neurodegenerative diseases[J]. Biochimica et Biophysica Acta(BBA)-Molecular Basis of Disease,2010,1802(1):151-161.
• [4]TURNER C,SCHAPIRA A H V. Mitochondrial matters of the brain:the role in Huntington’s disease[J]. Journal of Bioenergetics and Biomembranes,2010,42(3):193-198.
• [5]JIN J,ALBERTZ J,GUO Z,et al. Neuroprotective effects of PPAR-γagonist rosiglitazone in N171-82Q mouse model of Huntington's disease[J]. Journal of Neurochemistry,2013,125(3):410-419.
• [6]官志忠,高勤,桂传枝,等.慢性氟中毒脑损伤机制探讨[J].中国地方病学杂志,2011,30(3):352-354.
• [7]魏娜.慢性氟中毒对神经系统发育的影响[J].中华地方病学杂志,2013,32(3):347-350.
• [8]桂传枝,冉龙艳,官志忠.燃煤型氟中毒仔鼠大脑皮质超微结构改变[J].中国公共卫生,2011,27(11):393-393.
• [9]初可嘉,王海慧,吴迪,等.燃煤污染型氟中毒仔鼠成釉细胞损伤模型的建立[J].中华地方病学杂志,2016,35(2):105-109.
• [10]黄长青.地方性氟中毒的临床表现及与放射学改变关系的对比分析[C].中华医学会地方病学分会全国氟砷中毒学术会议,2005.
• [11]邱志伟,刘艳洁,官志忠.细胞外信号调节蛋白激酶5在慢性氟中毒大鼠脑组织中的表达及其与大鼠记忆力改变的关系[J].中华地方病学杂志,2016,35(2):94-98.
• [12]SCARPUUA R C. 7Ihnscriptional paradigms in mammalian mitochondrial biogenesis and function[J]. Physiol Rev,2008,88:611-638.
• [13]SCARPUUA R C. Nuclear control of respiratory chain expression by nuclear respiratory factors and PGC-l-related coactivator[J]. Ann NY Acad sci,2008,1147:321-334.
• [14]TRITOS N A,MASTAITIS J W,KOKKOTOU E G,et al. Characterization of the peroxisome proliferator activated receptor coactivator 1 alpha(PGC 1alpha)expression in the murine brain[J]. Brain Res,2003,961(2):255-260.
• [15]GUBEUINI P,PICCONI B,DI FILIPPO M,et al.Downstream mechanisms triggered by mitochondrial dysfunction in the basal ganglia:From experimental models to neurodegenerative diseases[J]. Biochim Biophys Acta,2010,1802:151-161.
• [16]EBRAHIM A S,KO L,YEN S. Reduced expression of peroxisome-proliferator activated receptor gamma coactivator-1αenhancesα-synuclein oligomerization and down regulates AKT/GSK3βsignaling pathway in human neuronal cells that inducibly expressα-synuclein[J]. Neuroscience Letters,2010,473(2):120-125.
• [17]HSU L J,SAGARA Y,ARROYO A,et al.α-Synuclein promotes mitochondrial deficit and oxidative stress[J].American Journal of Pathology,2000,157(2):401-410.
• [18]QIN W,HAROUTUNIAN V,KATSEL P,et al. PGC-1αexpression decreases in the Alzheimer disease brain as a function of dementia[J]. Archives of Neurology,2009,66(3):352.

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