Ras/Raf/ERK1/2信号通路在自闭症发病机制中的研究
发布时间：2020-12-06 11:12
自闭症谱系障碍（Autism Spectrum Disorders, ASD）是常见的神经系统发育失调导致的广泛性发展障碍。一般于儿童期（3岁以前）发病,以社交障碍、沟通能力缺陷以及重复刻板动作为主要临床特征。流行病学研究报道ASD发病率约为6/1000到10/1000,且近年发病率有上升趋势。目前我国国内ASD发病率尚无大规模流行病学统计资料,但根据目前其他国家的发病率,保守估计中国目前至少有100万ASD患者。目前认为,ASD是环境因素与遗传易感性共同作用的结果。而宫内环境是最重要的环境因素之一,因此自闭症亦被称为“胎源性疾病”。研究发现胚胎发育早期,即受精后20至40天的器官形成期为自闭症发病的易感期。如果在此期间胚胎受药物、重金属或母体不良状况等宫内环境因素的影响,胚胎未来发生自闭症的风险显著升高。Ras/Raf/ERKl/2 （extracellular signal-regulated kinase）信号通路是丝裂原活化蛋白激酶家族（mitogen-activated protein kinases, MAPKs）成员,对神经前体细胞的生成、神经脊的形成和发育、突触信号传递...
【文章来源】：南方医科大学广东省
【文章页数】：152 页
【学位级别】：博士
【部分图文】：
大脑皮质及小脑组织中RAS蛋白表达水平Figurel一1RelativeexPressionsofRASProteininhumaneortexandeerebellum
活性显著高于对照，我们推测磷酸化MEKI/2蛋白含量亦相应升高。认飞 Stemblot结果显示，自闭症患儿大脑皮质磷酸化/活化的MEKI/2蛋白含量比对照增加19.63%(t=一6.315，p<0.001，图1一5)，而MEKI/2总蛋白含量无显著变化(t=1.590， p=0.143)。使用磷酸化MEKI/2抗体进行的免疫组化染色的结果与 Westemblot结果吻合，自闭症患儿大脑皮质阳性神经元数量显著多于对照(t=5.320， P<0.001，图1一6)。此外，我们还检测了自闭症患儿小脑组织中MEKI/2总蛋白和磷酸化蛋白的含量，但与对照组相比无统计学差异(P>0.os)。
鲁COmlOI户目dsmCO日份.】A功i弓m图1一5大脑皮质中p一MEK及MEK蛋白表达水平Figurel一 5RelativeexPressionsofP一 MEKandMEKinhumaneortex户漪二鹭尹_一.尹、一万一类~扩蠢嘛分;嘿梦象，-争哪戳孰蜂缪笋之敏谬礴AutismControl humaneortexP一MEK60P<O00140UO工切的匀﹂dXnU，‘闰一一忿一口奋月习AUtismContFOI图1一6使用p一MEK抗体进行免疫组化染色结果(10x40)Figurel一 6ImmunostainingusingP一 MEKantibody(10X40)l6
【参考文献】：
期刊论文
[1]Efficacy of combined inhibition of mTOR and ERK/MAPK pathways in treating a tuberous sclerosis complex cell model[J]. Ruifang Mi a, b, Jianhui Ma a, Dechang Zhang c, Limin Li b, Hongbing Zhang a, * a Department of Physiology, Institute of Basic Medical Sciences and School of Basic Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100005, China b Department of Pathology, Institute of Basic Medical Sciences and School of Basic Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100005, China c Department of Pharmacology, Institute of Basic Medical Sciences and School of Basic Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100005, China. 遗传学报. 2009(06)
[2]Association of combined CYP2E1 gene polymorphism with the risk for esophageal squamous cell carcinoma in Huai’an population,China[J]. LIU Ran YIN Li-hong PU Yue-pu School of Public Health,Southeast University,Nanjing 210009,China (Liu R,Yin LH and Pu YP). Chinese Medical Journal. 2007(20)
[3]症状隐匿的局灶性癫痫与CASPR2突变[J]. Strauss K.A.,Puffenberger E.G.,Huentelman M.J.,郭俊. 世界核心医学期刊文摘(神经病学分册). 2006(08)
[4]孤独症儿童胃肠道症状与普通食物蛋白刺激所产生的细胞因子产量之间的关系评价[J]. Jyonouchi H.,Ruby A.,李丹. 世界核心医学期刊文摘(儿科学分册). 2005(10)
[5]The involvement of p38 MAPK in transforming growth factor β1-induced apoptosis in murine hepatocytes[J]. LIAO JIN HUI, JUN SONG CHEN, MIN QIANG CHAI, SHENG ZHAO, JIAN GUO SONG State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yue Yang Road, Shan. Cell Research. 2001(02)
本文编号：2901267
【文章来源】：南方医科大学广东省
【文章页数】：152 页
【学位级别】：博士
【部分图文】：
大脑皮质及小脑组织中RAS蛋白表达水平Figurel一1RelativeexPressionsofRASProteininhumaneortexandeerebellum
活性显著高于对照，我们推测磷酸化MEKI/2蛋白含量亦相应升高。认飞 Stemblot结果显示，自闭症患儿大脑皮质磷酸化/活化的MEKI/2蛋白含量比对照增加19.63%(t=一6.315，p<0.001，图1一5)，而MEKI/2总蛋白含量无显著变化(t=1.590， p=0.143)。使用磷酸化MEKI/2抗体进行的免疫组化染色的结果与 Westemblot结果吻合，自闭症患儿大脑皮质阳性神经元数量显著多于对照(t=5.320， P<0.001，图1一6)。此外，我们还检测了自闭症患儿小脑组织中MEKI/2总蛋白和磷酸化蛋白的含量，但与对照组相比无统计学差异(P>0.os)。
鲁COmlOI户目dsmCO日份.】A功i弓m图1一5大脑皮质中p一MEK及MEK蛋白表达水平Figurel一 5RelativeexPressionsofP一 MEKandMEKinhumaneortex户漪二鹭尹_一.尹、一万一类~扩蠢嘛分;嘿梦象，-争哪戳孰蜂缪笋之敏谬礴AutismControl humaneortexP一MEK60P<O00140UO工切的匀﹂dXnU，‘闰一一忿一口奋月习AUtismContFOI图1一6使用p一MEK抗体进行免疫组化染色结果(10x40)Figurel一 6ImmunostainingusingP一 MEKantibody(10X40)l6
【参考文献】：
期刊论文
[1]Efficacy of combined inhibition of mTOR and ERK/MAPK pathways in treating a tuberous sclerosis complex cell model[J]. Ruifang Mi a, b, Jianhui Ma a, Dechang Zhang c, Limin Li b, Hongbing Zhang a, * a Department of Physiology, Institute of Basic Medical Sciences and School of Basic Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100005, China b Department of Pathology, Institute of Basic Medical Sciences and School of Basic Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100005, China c Department of Pharmacology, Institute of Basic Medical Sciences and School of Basic Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100005, China. 遗传学报. 2009(06)
[2]Association of combined CYP2E1 gene polymorphism with the risk for esophageal squamous cell carcinoma in Huai’an population,China[J]. LIU Ran YIN Li-hong PU Yue-pu School of Public Health,Southeast University,Nanjing 210009,China (Liu R,Yin LH and Pu YP). Chinese Medical Journal. 2007(20)
[3]症状隐匿的局灶性癫痫与CASPR2突变[J]. Strauss K.A.,Puffenberger E.G.,Huentelman M.J.,郭俊. 世界核心医学期刊文摘(神经病学分册). 2006(08)
[4]孤独症儿童胃肠道症状与普通食物蛋白刺激所产生的细胞因子产量之间的关系评价[J]. Jyonouchi H.,Ruby A.,李丹. 世界核心医学期刊文摘(儿科学分册). 2005(10)
[5]The involvement of p38 MAPK in transforming growth factor β1-induced apoptosis in murine hepatocytes[J]. LIAO JIN HUI, JUN SONG CHEN, MIN QIANG CHAI, SHENG ZHAO, JIAN GUO SONG State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yue Yang Road, Shan. Cell Research. 2001(02)
本文编号：2901267
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