【摘要】：近年來,隨著人們認(rèn)識到脂肪細(xì)胞與肥胖及相關(guān)疾病息息相關(guān),人們對脂肪細(xì)胞的研究的興趣迎來飛躍性的增長,特別是在過去幾年,科研工作者發(fā)現(xiàn)了除白色脂肪細(xì)胞和棕色脂肪細(xì)胞之外的第三種脂肪細(xì)胞,即米色脂肪細(xì)胞,對脂肪細(xì)胞發(fā)育和分裂分化過程有了更加深入的認(rèn)識。肥胖與脂肪細(xì)胞的甘油三酯累積密切相關(guān),研究發(fā)現(xiàn),白色脂肪細(xì)胞(主要功能是儲存脂肪)在特定作用下分化為具有產(chǎn)熱作用且消耗自身甘油三酯的米色脂肪細(xì)胞,這種轉(zhuǎn)化途徑引起了廣泛關(guān)注。白色脂肪細(xì)胞轉(zhuǎn)化為米色脂肪細(xì)胞是由多因子調(diào)控的,研究白色脂肪細(xì)胞或者前脂肪細(xì)胞分化為米色脂肪細(xì)胞的關(guān)鍵調(diào)控基因,發(fā)現(xiàn)分化過程中的重要轉(zhuǎn)錄因子,將為肥胖疾病和相關(guān)代謝疾病的治療提供重要的理論依據(jù)。泛醌細(xì)胞色素 c 還原酶 1 基因(Ubiquinol-cytochrome c reductase core protein 1,Uqcrc1),編碼線粒體呼吸作用復(fù)合體Ⅲ(呼吸鏈的重要組成部分)的一個亞基。線粒體在棕色脂肪細(xì)胞和米色脂肪細(xì)胞產(chǎn)熱過程中起著關(guān)鍵作用。因此,本文以經(jīng)典的體外細(xì)胞模型--前體脂肪細(xì)胞系3T3-L1作為研究載體,利用慢病毒介導(dǎo)的RNA干擾(RNA interference,RNAi)技術(shù)抑制前脂肪細(xì)胞3T3-L1的Uqcrc1基因,并利用廣泛使用的雞尾酒法(地塞米松、胰島素和3-異丁基-1-甲基黃嘌呤)誘導(dǎo)前體脂肪細(xì)胞3T3-L1分化為白色脂肪細(xì)胞,并利用藥物組合(胰島素,3-異丁基-1-甲基黃嘌呤,羅格利酮,異丙腎上腺素)將白色脂肪轉(zhuǎn)化為米色脂肪細(xì)胞,來研究3T3-L1分化為米色脂肪細(xì)胞的潛能及Uqcrc1基因在脂肪細(xì)胞分化過程中的作用。實(shí)驗(yàn)結(jié)果顯示,與對照組相比較,經(jīng)攜帶干擾序列的慢病毒感染的3T3-L1細(xì)胞的基因Uqcrc1表達(dá)量大約降低了 90%。通過對比分化成熟的3T3-L1細(xì)胞中脂肪標(biāo)記基因Fabp4表達(dá)量的差異以及油紅染色結(jié)果,筆者發(fā)現(xiàn),抑制了3T3-L1的Uqcrc1基因后,細(xì)胞分化效率降低,脂滴積累減少,分化潛能被抑制。誘導(dǎo)3T3-L1形成米色脂肪細(xì)胞的實(shí)驗(yàn)中,細(xì)胞中關(guān)鍵產(chǎn)熱基因Ucp1(解偶聯(lián)蛋白),關(guān)鍵轉(zhuǎn)錄控制因子基因C/EBPβ Prdm16,Pgc-1 以及米色脂肪細(xì)胞標(biāo)記基因Cd137,Cited1,Tmem26,Tbx1表達(dá)量均有顯著性升高;利用慢病毒系統(tǒng)抑制3T3-L1細(xì)胞中Uqcrc1基因后,以上基因均顯著性低于對照組。因此,抑制Uqcrc1基因表達(dá)在一定程度上抑制了白色脂肪細(xì)胞分化及其棕樣化。根據(jù)以上結(jié)果,Uqcrc1基因在白色脂肪生成以及白色脂肪細(xì)胞棕樣化扮演的重要角色,為肥胖治療及其潛能提供了依據(jù)。
[Abstract]:In recent years, with the realization that adipocytes are closely related to obesity and related diseases, interest in adipocyte research has grown dramatically, especially in the past few years. Researchers have discovered that the third kind of adipocytes, beige adipocytes, besides white adipocytes and brown adipocytes, have a deeper understanding of adipocyte development and differentiation. Obesity is closely related to the accumulation of triglycerides in adipocytes. Studies have found that white fat cells (the main function of which is to store fat) differentiate into beige fat cells that produce heat and consume their own triglycerides. This way of transformation has aroused widespread concern. The transformation of white adipocytes into beige adipocytes is regulated by multiple factors. The key regulatory genes for the differentiation of white adipocytes or preadipocytes into beige adipocytes were studied, and the important transcription factors in the process of differentiation were found. It will provide important theoretical basis for the treatment of obesity and related metabolic diseases. Ubiquinone cytochrome c reductase 1 (Ubiquinol-cytochrome c reductase core protein 1) is a subunit encoding mitochondrial respiratory complex 鈪，

本文編號：2190217