本文主要研究内容
作者李娇妹（2019）在《n-3多不饱和脂肪酸对乳腺癌发病风险的影响及其作用机制》一文中研究指出：n-3 多不饱和脂肪酸(n-3 polyunsaturated fatty acid;n-3PUFA)是指第一个双键出现在碳链甲基端第三个碳位的含两个或两个以上双键的多聚多不饱和脂肪酸,在人体中发挥着重要的生理功能。研究表明,n-3 PUFA对高血压、2型糖尿病、癌症和非酒精性脂肪肝等慢性疾病的发生发展具有一定的保护作用。其中,n-3 PUFA与乳腺癌的关系一直存在争议,虽然动物实验及体外实验显示n-3 PUFA具有良好的抗乳腺癌功效,但是来自流行病学的研究结果并不一致,且缺乏来自中国人群的有力证据。为明确n-3 PUFA与乳腺癌的关系及作用机理,本课题通过病例-对照试验探究了中国女性红细胞磷脂n-3 PUFA与乳腺癌的关系并分析了恶性和良性乳腺肿瘤组织中小分子代谢物的差异;通过动物实验模型探究了孕期摄入n-3 PUFA对子代乳腺癌发病风险的影响及作用机制。本研究的主要结果如下:(1)在中国女性乳腺癌与磷脂n-3PUFA关系的流行病学研究中,我们采用病例对照的研究设计,纳入乳腺癌患者104人、良性肿瘤患者72人和健康对照70人。结果显示,与健康人群相比,乳腺癌患者和良性肿瘤患者体内红细胞磷脂脂肪酸C18:3 n-3、C20:5 n-3和总n-3 PUFA含量均显著降低。多元逻辑回归结果显示,n-3 PUFA含量与乳腺癌及良性乳腺肿瘤的发病率均呈显著负相关。(2)在循环n-3 PUFA对恶性和良种乳腺肿瘤中小分子代谢物影响的研究中,我们纳入了 98例恶性肿瘤组织、66例良性肿瘤组织和27例健康乳腺组织。结果显示,有4个差异代谢物(牛磺酸、胆碱、L-氢化乳清酸和硬脂酸酰胺)在恶性肿瘤组织中的含量显著高于在良性肿瘤组织中的含量,后者也高于在健康乳腺组织中的含量,有2个差异代谢物(溶血磷脂酰]8:3n-3和溶血磷脂酰22:6n-3)的含量在恶性肿瘤组织中低于在良性肿瘤组织中,后者又低于在健康乳腺组织中的含量。这些物质主要参与磷脂和脂质代谢,因此提示磷脂和脂质代谢紊乱是n-3 PUFA缺乏导致乳腺疾病恶化的代谢机理。(3)在动物实验中,我们将40只8周龄雌性C57BL/6J孕鼠随机分为四组,分别用低脂标准饲料(Control)、高脂红花油饲料(SO)、高脂鱼油饲料(FO)和高脂亚麻籽油饲料(FSO)干预6周(3周妊娠期+3周哺乳期)。待子代小鼠断奶以后,母亲和子代小鼠均开始摄入AIN-92G标准饲料。用二甲基苯并蒽DMBA对7周龄雌性子代进行乳腺肿瘤模型诱导。结果表明,与Control组子代小鼠相比,孕期高脂饮食显著增加DMBA诱导的乳腺肿瘤发病率。与SO组子代小鼠相比,FO和FSO组子代的乳腺肿瘤发病率显著降低。在未进行造模处理的子代小鼠中,与SO组相比,FO组和FSO组子代的乳腺组织终末芽孢数量,血清雌二醇(17β-estradiol)含量和乳腺细胞增殖率均显著降低,乳腺细胞凋亡率显著升高,青春期到来时间显著延迟。表明母亲妊娠期和哺乳期摄入动物或植物来源的n-3 PUFA,均能显著降低子代乳腺肿瘤的患病风险。(4)在动物实验中,我们利用fat-l转基因小鼠和野生型C57BL/6J小鼠模型,探究母亲内源性n-3PUFA降低子代乳腺癌风险的作用机理。两组小鼠妊娠期均统一饲喂n-6 PUFA高脂饲料,比较两组的野生型雌性子代的乳腺癌发病风险。结果表明,DMBA药物刺激后,fat-1组小鼠子代的乳腺肿瘤发病率显著低于野生对照组。Fat-l孕鼠内源性合成的n-3 PUFA改变了子代乳腺组织中的长链非编码RNA(longnoncodingRNA.lncRNA)的表达,与对照组相比,fat-1组子代小鼠乳腺组织中有53条IncRNA表达上调和45条IncRNA表达下调。差异表达的IncRNA可以调节多条与肿瘤发生发展相关的信号通路中mRNA的表达,尤其是NF-κB,Jak-STAT和MAPK信号通路。这些通路中的关键蛋白,如p65,p60,STAT3,Jakl和p38在.fat-l组子代中的表达显著降低。同时,与对照组相比,fat-1组子代乳腺组织具有显著降低的细胞增殖率和显著升高的细胞凋亡率。表明母亲孕期内源性合成n-3 PUFA降低子代乳腺癌的易感性与其对子代乳腺组织中IncRNA表达的调控作用有关。综上所述,本研究通过人体病例对照试验发现磷脂C18:3 n-3、C20:5 n-3和总n-3 PUFA的缺乏及磷脂和脂质代谢紊乱均与乳腺癌的发生密切相关。动物实验发现母亲孕期摄入n-3 PUFA高脂饮食能降低子代乳腺癌的患病风险,其作用机理与长链非编码RNA的调控有关,后者通过调节NF-κB,Jak-STAT和MAPK信号通路中mRNA和关键蛋白的表达降低子代乳腺癌的易感性。
Abstract
n-3 duo bu bao he zhi fang suan (n-3 polyunsaturated fatty acid;n-3PUFA)shi zhi di yi ge shuang jian chu xian zai tan lian jia ji duan di san ge tan wei de han liang ge huo liang ge yi shang shuang jian de duo ju duo bu bao he zhi fang suan ,zai ren ti zhong fa hui zhao chong yao de sheng li gong neng 。yan jiu biao ming ,n-3 PUFAdui gao xie ya 、2xing tang niao bing 、ai zheng he fei jiu jing xing zhi fang gan deng man xing ji bing de fa sheng fa zhan ju you yi ding de bao hu zuo yong 。ji zhong ,n-3 PUFAyu ru xian ai de guan ji yi zhi cun zai zheng yi ,sui ran dong wu shi yan ji ti wai shi yan xian shi n-3 PUFAju you liang hao de kang ru xian ai gong xiao ,dan shi lai zi liu hang bing xue de yan jiu jie guo bing bu yi zhi ,ju que fa lai zi zhong guo ren qun de you li zheng ju 。wei ming que n-3 PUFAyu ru xian ai de guan ji ji zuo yong ji li ,ben ke ti tong guo bing li -dui zhao shi yan tan jiu le zhong guo nv xing gong xi bao lin zhi n-3 PUFAyu ru xian ai de guan ji bing fen xi le e xing he liang xing ru xian zhong liu zu zhi zhong xiao fen zi dai xie wu de cha yi ;tong guo dong wu shi yan mo xing tan jiu le yun ji she ru n-3 PUFAdui zi dai ru xian ai fa bing feng xian de ying xiang ji zuo yong ji zhi 。ben yan jiu de zhu yao jie guo ru xia :(1)zai zhong guo nv xing ru xian ai yu lin zhi n-3PUFAguan ji de liu hang bing xue yan jiu zhong ,wo men cai yong bing li dui zhao de yan jiu she ji ,na ru ru xian ai huan zhe 104ren 、liang xing zhong liu huan zhe 72ren he jian kang dui zhao 70ren 。jie guo xian shi ,yu jian kang ren qun xiang bi ,ru xian ai huan zhe he liang xing zhong liu huan zhe ti nei gong xi bao lin zhi zhi fang suan C18:3 n-3、C20:5 n-3he zong n-3 PUFAhan liang jun xian zhe jiang di 。duo yuan luo ji hui gui jie guo xian shi ,n-3 PUFAhan liang yu ru xian ai ji liang xing ru xian zhong liu de fa bing lv jun cheng xian zhe fu xiang guan 。(2)zai xun huan n-3 PUFAdui e xing he liang chong ru xian zhong liu zhong xiao fen zi dai xie wu ying xiang de yan jiu zhong ,wo men na ru le 98li e xing zhong liu zu zhi 、66li liang xing zhong liu zu zhi he 27li jian kang ru xian zu zhi 。jie guo xian shi ,you 4ge cha yi dai xie wu (niu huang suan 、dan jian 、L-qing hua ru qing suan he ying zhi suan xian an )zai e xing zhong liu zu zhi zhong de han liang xian zhe gao yu zai liang xing zhong liu zu zhi zhong de han liang ,hou zhe ye gao yu zai jian kang ru xian zu zhi zhong de han liang ,you 2ge cha yi dai xie wu (rong xie lin zhi xian ]8:3n-3he rong xie lin zhi xian 22:6n-3)de han liang zai e xing zhong liu zu zhi zhong di yu zai liang xing zhong liu zu zhi zhong ,hou zhe you di yu zai jian kang ru xian zu zhi zhong de han liang 。zhe xie wu zhi zhu yao can yu lin zhi he zhi zhi dai xie ,yin ci di shi lin zhi he zhi zhi dai xie wen luan shi n-3 PUFAque fa dao zhi ru xian ji bing e hua de dai xie ji li 。(3)zai dong wu shi yan zhong ,wo men jiang 40zhi 8zhou ling ci xing C57BL/6Jyun shu sui ji fen wei si zu ,fen bie yong di zhi biao zhun si liao (Control)、gao zhi gong hua you si liao (SO)、gao zhi yu you si liao (FO)he gao zhi ya ma zi you si liao (FSO)gan yu 6zhou (3zhou ren shen ji +3zhou bu ru ji )。dai zi dai xiao shu duan nai yi hou ,mu qin he zi dai xiao shu jun kai shi she ru AIN-92Gbiao zhun si liao 。yong er jia ji ben bing en DMBAdui 7zhou ling ci xing zi dai jin hang ru xian zhong liu mo xing you dao 。jie guo biao ming ,yu Controlzu zi dai xiao shu xiang bi ,yun ji gao zhi yin shi xian zhe zeng jia DMBAyou dao de ru xian zhong liu fa bing lv 。yu SOzu zi dai xiao shu xiang bi ,FOhe FSOzu zi dai de ru xian zhong liu fa bing lv xian zhe jiang di 。zai wei jin hang zao mo chu li de zi dai xiao shu zhong ,yu SOzu xiang bi ,FOzu he FSOzu zi dai de ru xian zu zhi zhong mo ya bao shu liang ,xie qing ci er chun (17β-estradiol)han liang he ru xian xi bao zeng shi lv jun xian zhe jiang di ,ru xian xi bao diao wang lv xian zhe sheng gao ,qing chun ji dao lai shi jian xian zhe yan chi 。biao ming mu qin ren shen ji he bu ru ji she ru dong wu huo zhi wu lai yuan de n-3 PUFA,jun neng xian zhe jiang di zi dai ru xian zhong liu de huan bing feng xian 。(4)zai dong wu shi yan zhong ,wo men li yong fat-lzhuai ji yin xiao shu he ye sheng xing C57BL/6Jxiao shu mo xing ,tan jiu mu qin nei yuan xing n-3PUFAjiang di zi dai ru xian ai feng xian de zuo yong ji li 。liang zu xiao shu ren shen ji jun tong yi si wei n-6 PUFAgao zhi si liao ,bi jiao liang zu de ye sheng xing ci xing zi dai de ru xian ai fa bing feng xian 。jie guo biao ming ,DMBAyao wu ci ji hou ,fat-1zu xiao shu zi dai de ru xian zhong liu fa bing lv xian zhe di yu ye sheng dui zhao zu 。Fat-lyun shu nei yuan xing ge cheng de n-3 PUFAgai bian le zi dai ru xian zu zhi zhong de chang lian fei bian ma RNA(longnoncodingRNA.lncRNA)de biao da ,yu dui zhao zu xiang bi ,fat-1zu zi dai xiao shu ru xian zu zhi zhong you 53tiao IncRNAbiao da shang diao he 45tiao IncRNAbiao da xia diao 。cha yi biao da de IncRNAke yi diao jie duo tiao yu zhong liu fa sheng fa zhan xiang guan de xin hao tong lu zhong mRNAde biao da ,you ji shi NF-κB,Jak-STAThe MAPKxin hao tong lu 。zhe xie tong lu zhong de guan jian dan bai ,ru p65,p60,STAT3,Jaklhe p38zai .fat-lzu zi dai zhong de biao da xian zhe jiang di 。tong shi ,yu dui zhao zu xiang bi ,fat-1zu zi dai ru xian zu zhi ju you xian zhe jiang di de xi bao zeng shi lv he xian zhe sheng gao de xi bao diao wang lv 。biao ming mu qin yun ji nei yuan xing ge cheng n-3 PUFAjiang di zi dai ru xian ai de yi gan xing yu ji dui zi dai ru xian zu zhi zhong IncRNAbiao da de diao kong zuo yong you guan 。zeng shang suo shu ,ben yan jiu tong guo ren ti bing li dui zhao shi yan fa xian lin zhi C18:3 n-3、C20:5 n-3he zong n-3 PUFAde que fa ji lin zhi he zhi zhi dai xie wen luan jun yu ru xian ai de fa sheng mi qie xiang guan 。dong wu shi yan fa xian mu qin yun ji she ru n-3 PUFAgao zhi yin shi neng jiang di zi dai ru xian ai de huan bing feng xian ,ji zuo yong ji li yu chang lian fei bian ma RNAde diao kong you guan ,hou zhe tong guo diao jie NF-κB,Jak-STAThe MAPKxin hao tong lu zhong mRNAhe guan jian dan bai de biao da jiang di zi dai ru xian ai de yi gan xing 。
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论文作者分别是来自浙江大学的李娇妹，发表于刊物浙江大学2019-04-12论文，是一篇关于乳腺癌论文,代谢组学论文,孕期营养论文,表观遗传学论文,浙江大学2019-04-12论文的文章。本文可供学术参考使用，各位学者可以免费参考阅读下载，文章观点不代表本站观点，资料来自浙江大学2019-04-12论文网站，若本站收录的文献无意侵犯了您的著作版权，请联系我们删除。
标签：乳腺癌论文; 代谢组学论文; 孕期营养论文; 表观遗传学论文; 浙江大学2019-04-12论文;