Ras/Raf/ERK1/2信號(hào)通路在自閉癥發(fā)病機(jī)制中的研究
發(fā)布時(shí)間：2020-12-06 11:12
自閉癥譜系障礙（Autism Spectrum Disorders, ASD）是常見的神經(jīng)系統(tǒng)發(fā)育失調(diào)導(dǎo)致的廣泛性發(fā)展障礙。一般于兒童期（3歲以前）發(fā)病,以社交障礙、溝通能力缺陷以及重復(fù)刻板動(dòng)作為主要臨床特征。流行病學(xué)研究報(bào)道ASD發(fā)病率約為6/1000到10/1000,且近年發(fā)病率有上升趨勢(shì)。目前我國(guó)國(guó)內(nèi)ASD發(fā)病率尚無大規(guī)模流行病學(xué)統(tǒng)計(jì)資料,但根據(jù)目前其他國(guó)家的發(fā)病率,保守估計(jì)中國(guó)目前至少有100萬ASD患者。目前認(rèn)為,ASD是環(huán)境因素與遺傳易感性共同作用的結(jié)果。而宮內(nèi)環(huán)境是最重要的環(huán)境因素之一,因此自閉癥亦被稱為“胎源性疾病”。研究發(fā)現(xiàn)胚胎發(fā)育早期,即受精后20至40天的器官形成期為自閉癥發(fā)病的易感期。如果在此期間胚胎受藥物、重金屬或母體不良狀況等宮內(nèi)環(huán)境因素的影響,胚胎未來發(fā)生自閉癥的風(fēng)險(xiǎn)顯著升高。Ras/Raf/ERKl/2 （extracellular signal-regulated kinase）信號(hào)通路是絲裂原活化蛋白激酶家族（mitogen-activated protein kinases, MAPKs）成員,對(duì)神經(jīng)前體細(xì)胞的生成、神經(jīng)脊的形成和發(fā)育、突觸信號(hào)傳遞...
【文章來源】：南方醫(yī)科大學(xué)廣東省
【文章頁(yè)數(shù)】：152 頁(yè)
【學(xué)位級(jí)別】：博士
【部分圖文】：
大腦皮質(zhì)及小腦組織中RAS蛋白表達(dá)水平Figurel一1RelativeexPressionsofRASProteininhumaneortexandeerebellum
活性顯著高于對(duì)照，我們推測(cè)磷酸化MEKI/2蛋白含量亦相應(yīng)升高。認(rèn)飛 Stemblot結(jié)果顯示，自閉癥患兒大腦皮質(zhì)磷酸化/活化的MEKI/2蛋白含量比對(duì)照增加19.63%(t=一6.315，p<0.001，圖1一5)，而MEKI/2總蛋白含量無顯著變化(t=1.590， p=0.143)。使用磷酸化MEKI/2抗體進(jìn)行的免疫組化染色的結(jié)果與 Westemblot結(jié)果吻合，自閉癥患兒大腦皮質(zhì)陽(yáng)性神經(jīng)元數(shù)量顯著多于對(duì)照(t=5.320， P<0.001，圖1一6)。此外，我們還檢測(cè)了自閉癥患兒小腦組織中MEKI/2總蛋白和磷酸化蛋白的含量，但與對(duì)照組相比無統(tǒng)計(jì)學(xué)差異(P>0.os)。
魯COmlOI戶目dsmCO日份.】A功i弓m圖1一5大腦皮質(zhì)中p一MEK及MEK蛋白表達(dá)水平Figurel一 5RelativeexPressionsofP一 MEKandMEKinhumaneortex戶漪二鷺尹_一.尹、一萬一類~擴(kuò)蠢嘛分;嘿夢(mèng)象，-爭(zhēng)哪戳孰蜂繆筍之敏謬礴AutismControl humaneortexP一MEK60P<O00140UO工切的勻﹂dXnU，‘閏一一忿一口奮月習(xí)AUtismContFOI圖1一6使用p一MEK抗體進(jìn)行免疫組化染色結(jié)果(10x40)Figurel一 6ImmunostainingusingP一 MEKantibody(10X40)l6
【參考文獻(xiàn)】：
期刊論文
[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. 遺傳學(xué)報(bào). 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]癥狀隱匿的局灶性癲癇與CASPR2突變[J]. Strauss K.A.,Puffenberger E.G.,Huentelman M.J.,郭俊. 世界核心醫(yī)學(xué)期刊文摘(神經(jīng)病學(xué)分冊(cè)). 2006(08)
[4]孤獨(dú)癥兒童胃腸道癥狀與普通食物蛋白刺激所產(chǎn)生的細(xì)胞因子產(chǎn)量之間的關(guān)系評(píng)價(jià)[J]. Jyonouchi H.,Ruby A.,李丹. 世界核心醫(yī)學(xué)期刊文摘(兒科學(xué)分冊(cè)). 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)
本文編號(hào)：2901267
【文章來源】：南方醫(yī)科大學(xué)廣東省
【文章頁(yè)數(shù)】：152 頁(yè)
【學(xué)位級(jí)別】：博士
【部分圖文】：
大腦皮質(zhì)及小腦組織中RAS蛋白表達(dá)水平Figurel一1RelativeexPressionsofRASProteininhumaneortexandeerebellum
活性顯著高于對(duì)照，我們推測(cè)磷酸化MEKI/2蛋白含量亦相應(yīng)升高。認(rèn)飛 Stemblot結(jié)果顯示，自閉癥患兒大腦皮質(zhì)磷酸化/活化的MEKI/2蛋白含量比對(duì)照增加19.63%(t=一6.315，p<0.001，圖1一5)，而MEKI/2總蛋白含量無顯著變化(t=1.590， p=0.143)。使用磷酸化MEKI/2抗體進(jìn)行的免疫組化染色的結(jié)果與 Westemblot結(jié)果吻合，自閉癥患兒大腦皮質(zhì)陽(yáng)性神經(jīng)元數(shù)量顯著多于對(duì)照(t=5.320， P<0.001，圖1一6)。此外，我們還檢測(cè)了自閉癥患兒小腦組織中MEKI/2總蛋白和磷酸化蛋白的含量，但與對(duì)照組相比無統(tǒng)計(jì)學(xué)差異(P>0.os)。
魯COmlOI戶目dsmCO日份.】A功i弓m圖1一5大腦皮質(zhì)中p一MEK及MEK蛋白表達(dá)水平Figurel一 5RelativeexPressionsofP一 MEKandMEKinhumaneortex戶漪二鷺尹_一.尹、一萬一類~擴(kuò)蠢嘛分;嘿夢(mèng)象，-爭(zhēng)哪戳孰蜂繆筍之敏謬礴AutismControl humaneortexP一MEK60P<O00140UO工切的勻﹂dXnU，‘閏一一忿一口奮月習(xí)AUtismContFOI圖1一6使用p一MEK抗體進(jìn)行免疫組化染色結(jié)果(10x40)Figurel一 6ImmunostainingusingP一 MEKantibody(10X40)l6
【參考文獻(xiàn)】：
期刊論文
[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. 遺傳學(xué)報(bào). 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]癥狀隱匿的局灶性癲癇與CASPR2突變[J]. Strauss K.A.,Puffenberger E.G.,Huentelman M.J.,郭俊. 世界核心醫(yī)學(xué)期刊文摘(神經(jīng)病學(xué)分冊(cè)). 2006(08)
[4]孤獨(dú)癥兒童胃腸道癥狀與普通食物蛋白刺激所產(chǎn)生的細(xì)胞因子產(chǎn)量之間的關(guān)系評(píng)價(jià)[J]. Jyonouchi H.,Ruby A.,李丹. 世界核心醫(yī)學(xué)期刊文摘(兒科學(xué)分冊(cè)). 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)
本文編號(hào)：2901267
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