本文選題：非酒精性脂肪性肝病 + 內(nèi)質(zhì)網(wǎng)應(yīng)激��； 參考：《浙江大學(xué)》2014年碩士論文

【摘要】：目的：非酒精性脂肪性肝病(nonalcoholic fatty liver disease, NAFLD)是近年來(lái)影響人民生活健康的常見(jiàn)肝病之一。研究發(fā)現(xiàn),內(nèi)質(zhì)網(wǎng)應(yīng)激(endoplasmic reticulum stress, ERS)在NAFLD發(fā)生發(fā)展過(guò)程中發(fā)揮重要作用,其確切分子機(jī)制尚未明確。本課題旨在分析內(nèi)質(zhì)網(wǎng)分子伴侶蛋白質(zhì)二硫鍵異構(gòu)酶A3前體(protein disulfide isomerase A3precursor, PDIA3/ERp57)在NAFLD中的作用及分子機(jī)制。 方法：本研究運(yùn)用軟脂酸(palmitic acid, PA)誘導(dǎo)人正常肝細(xì)胞系L02細(xì)胞建立NAFLD細(xì)胞模型。在此基礎(chǔ)上,采用小分子RNA干擾(siRNA)、免疫印記、細(xì)胞凋亡檢測(cè)等分子生物學(xué)手段,系統(tǒng)研究?jī)?nèi)質(zhì)網(wǎng)分子伴侶PDIA3在NAFLD發(fā)生發(fā)展過(guò)程中的作用及分子機(jī)制。 結(jié)果：(1)用PA成功建立NAFLD細(xì)胞模型；(2)PDIA3在NAFLD細(xì)胞模型中表達(dá)上調(diào)；(3)NAFLD細(xì)胞模型中,siRNA抑制PDIA3表達(dá)后引起細(xì)胞脂變加重、凋亡增多；(4)NAFLD細(xì)胞模型中,siRNA抑制PDIA3表達(dá)后引起脂肪酸合成酶(fatty acid synthase, FAS)、磷酸化的PKR樣內(nèi)質(zhì)網(wǎng)調(diào)節(jié)激酶(phospho-PKR-like ER kinase, P-PERK)、葡萄糖調(diào)節(jié)蛋白78(glucose-regulatedprotein78, GRP78)和C/EBP同源蛋白(C/EBP homologous protein, CHOP)表達(dá)升高。 結(jié)論：(1)PDIA3參與NAFLD的發(fā)生發(fā)展；(2)PDIA3表達(dá)抑制通過(guò)上調(diào)FAS蛋白表達(dá)加重軟脂酸誘導(dǎo)的肝細(xì)胞脂肪變性；(3)PDIA3表達(dá)抑制通過(guò)激活PERK-CHOP通路加重軟脂酸誘導(dǎo)的肝細(xì)胞ERS及其相關(guān)凋亡。本課題的順利實(shí)施為深入認(rèn)識(shí)NAFLD的分子機(jī)制,發(fā)現(xiàn)新的診斷和治療靶標(biāo)提供了理論依據(jù)。
[Abstract]:Objective: nonalcoholic fatty liver disease (NAFLD) is one of the most common liver diseases affecting people's health in recent years. It is found that endoplasmic reticulum stress (ERSs) plays an important role in the development of NAFLD, and its exact molecular mechanism is not clear. The purpose of this study was to analyze the role and molecular mechanism of endoplasmic reticulum molecular chaperone protein disulfide isomerase A3 precursor. PDIA 3 / ERp57 in NAFLD. Methods: NAFLD cell model was induced by palmitic acidin (PAA) in human normal liver cell line L02. On this basis, the role and molecular mechanism of endoplasmic reticulum molecular chaperone PDIA3 in the pathogenesis and development of NAFLD were systematically studied by means of molecular biological methods such as small molecular RNA interference siRNAs, immunological imprinting and cell apoptosis detection. Results (1) NAFLD cell model was successfully established with PA. In NAFLD cell model, the expression of NAFLD was upregulated and increased after inhibiting the expression of PDIA3. The inhibition of PDIA3 expression by siRNA in NAFLD cell model resulted in the increased expression of fatty acid synthase (FASA), phospho-PKR-like kinase (P-PERKN), glucose-regulated protein 78 (GRP78) and C/EBP homologous protein C / EBP homologous protein, CHOP). Conclusion the inhibition of PDIA3 expression in NAFLD by up-regulating the expression of FAS protein increases the inhibition of PDIA3 expression in hepatocytes induced by palmitic acid. The inhibition of PDIA3 expression by activating the PERK-CHOP pathway can aggravate the ERS and its related apoptosis in hepatocytes induced by palmitic acid. The successful implementation of this project provides a theoretical basis for further understanding the molecular mechanism of NAFLD and finding new diagnostic and therapeutic targets.
【學(xué)位授予單位】：浙江大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2014
【分類號(hào)】：R575

【參考文獻(xiàn)】

相關(guān)期刊論文 前1條

1 中華醫(yī)學(xué)會(huì)肝臟病學(xué)分會(huì)脂肪肝和酒精性肝病學(xué)組;;非酒精性脂肪性肝病診療指南[J];中國(guó)肝臟病雜志(電子版);2010年04期

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本文編號(hào)：1820818