本文選題：鄰苯二甲酸酯類　切入點(diǎn)：肥胖　出處：《重慶醫(yī)科大學(xué)》2012年碩士論文　論文類型：學(xué)位論文

【摘要】：研究目的：脂肪細(xì)胞的增殖和分化異�？梢鹬炯�(xì)胞數(shù)目增多、體積變大、脂肪顆粒過多堆積，從而導(dǎo)致能量代謝平衡失調(diào)，引起肥胖及相關(guān)疾病，給社會經(jīng)濟(jì)發(fā)展帶來巨大經(jīng)濟(jì)負(fù)擔(dān)。環(huán)境因素是肥胖疾病的影響因素之一：鄰苯二甲酸酯類(PAEs）是一類持久性有機(jī)污染物，具有環(huán)境類雌激素樣作用，在人體內(nèi)已有較高暴露量。目前關(guān)于其毒性危害研究均集中在生殖毒性方面。文獻(xiàn)報道和前期研究提示PAEs與腹部肥胖以及兒童肥胖相關(guān)，但目前未見其影響機(jī)制的研究。 研究方法：本課題以PAEs是過氧化物酶體增殖劑為切入點(diǎn)，可以激活過氧化物酶體增殖劑受體PPARs。以兩種我國工業(yè)使用最多的、人體暴露量最高的兩種PAEs（DBP、DEHP）為研究目標(biāo)。采用體外培養(yǎng)小鼠來源的3T3-L1前體脂肪細(xì)胞建立實驗?zāi)Ｐ�，�?jīng)典激素雞尾酒法誘導(dǎo)3T3-L1前體脂肪細(xì)胞分化成成熟的脂肪細(xì)胞，設(shè)計兩種標(biāo)志性PAEs染毒參與3T3-L1前體脂肪細(xì)胞的誘導(dǎo)分化，采用油紅O染色法在倒置熒光顯微鏡下觀察細(xì)胞形態(tài)變化、脂滴的形成過程和脂滴數(shù)量變化；采用油紅O提取法定量分析脂肪細(xì)胞脂滴含量變化；采用實時熒光定量PCR技術(shù)分析分化基因PPARγ和脂聯(lián)素的表達(dá)變化。 研究結(jié)果：在誘導(dǎo)分化第二天后，，染毒組劑量組率先出現(xiàn)脂滴。誘導(dǎo)分化結(jié)束后染毒劑量組脂滴含量大于空白對照組，同時不同染毒劑量組脂滴含量隨染毒劑量遞增。脂肪細(xì)胞分化基因PPARγ、脂聯(lián)素均隨著染毒劑量的增加而表達(dá)上調(diào)(P0.01)。 研究結(jié)論：PAEs是脂肪細(xì)胞分化基因PPARγ的有效配體可以與之結(jié)合從而激活它，PPARγ參與脂肪細(xì)胞誘導(dǎo)分化過程。脂肪細(xì)胞分化基因PPARγ、脂聯(lián)素均表達(dá)上調(diào)，從而使3T3-L1前體脂肪細(xì)胞變成熟脂肪細(xì)胞數(shù)量增多，脂肪顆粒明顯增加。本研究結(jié)果為PAEs與肥胖的關(guān)系研究提供了一條新的思路，為相關(guān)公共衛(wèi)生政策的制定提供科學(xué)依據(jù)。并為未來肥胖疾病的防治及肥胖與環(huán)境污染關(guān)系的研究開辟新途徑。
[Abstract]:Objective: abnormal proliferation and differentiation of adipocytes can increase the number of adipocytes, increase the volume of adipocytes, accumulate too many fat particles, and lead to imbalance of energy metabolism, obesity and related diseases. Environmental factors are one of the influencing factors of obesity disease: phthalate ester (PAEs) is a kind of persistent organic pollutant, which has environmental estrogen-like effect. Studies on the toxicity of PAEs have been focused on reproductive toxicity. Literature reports and previous studies suggest that PAEs is associated with abdominal obesity and childhood obesity, but there is no study on the mechanism of its effects. Methods: in this study, PAEs is the peroxisome proliferator, which can activate the peroxisome proliferator receptor PPAR. The two kinds of PAESS DBP (DEHP), which were the most exposed to human body, were used to establish the experimental model of 3T3-L1 precursor adipocytes derived from mice in vitro. The 3T3-L1 precursor adipocytes were induced to differentiate into mature adipocytes by the classical hormone cocktail method. Two kinds of iconic PAEs were designed to induce the differentiation of 3T3-L1 precursor adipocytes. Oil red O staining was used to observe the morphological changes of the cells, the formation process of lipid droplets and the changes of the number of lipid droplets under inverted fluorescence microscope. The changes of lipid droplets in adipocytes were analyzed by oil red O extraction, and the expression of PPAR 緯 and adiponectin in adipocytes were analyzed by real-time fluorescence quantitative PCR. Results: after the second day of induced differentiation, lipid droplets appeared first in the dose group, and the lipid drop content in the dose group was higher than that in the blank control group after the induction of differentiation. The adipocyte differentiation gene PPAR 緯 and adiponectin were all up-regulated with the increase of dose of adipocyte differentiation gene PPAR 緯 and adiponectin. Conclusion PPAR 緯 is an effective ligand of adipocyte differentiation gene PPAR 緯, which can be activated to participate in adipocyte differentiation. The expression of adipocyte differentiation gene PPAR 緯 and adiponectin is up-regulated. As a result, 3T3-L1 precursor adipocytes increased the number of mature adipocytes and increased the number of fat particles. The results of this study provide a new idea for the study of the relationship between PAEs and obesity. It provides a scientific basis for the formulation of relevant public health policies and opens up a new way for the prevention and treatment of obesity diseases and the study of the relationship between obesity and environmental pollution in the future.
【學(xué)位授予單位】：重慶醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2012
【分類號】：R151

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