本文關(guān)鍵詞： NO-1886 膽固醇7α羥化酶 生長激素 胰島素樣生長因子-1 信號(hào)調(diào)節(jié)蛋白α1　出處：《南華大學(xué)》2006年碩士論文　論文類型：學(xué)位論文

【摘要】：目的：脂蛋白酯酶(lipoprotein lipase，LPL)活化劑NO-1886能夠通過下調(diào)血漿中脂質(zhì)、葡萄糖及提高胰島素敏感性而改善飲食誘導(dǎo)的2型糖尿病。但是具體的藥物作用機(jī)制目前并不清楚。本實(shí)驗(yàn)旨在細(xì)胞及整體水平上探討該化合物對(duì)生長激素(growth hormone，GH)信號(hào)通路中胰島素樣生長因子-1(insulin like growth factor-1，IGF-1)和膽固醇7α羥化酶(cholesterol 7α hydroxylase，CYP7A1)的作用，并初步探討其可能的作用機(jī)制。 方法：分別以人肝胚G2細(xì)胞株(human hepatoma blastoma G2 cells，HepG2 cells)和廣西巴馬小型豬(Guangxi Bama minipigs)為人肝臟細(xì)胞和動(dòng)物模型，采用免疫印跡法(immuno-blotting)檢測(cè)CYP7A1、信號(hào)調(diào)節(jié)蛋白α1(signaling regulatory protein α1，SIRPα1)、β-肌動(dòng)蛋白(β-actin)的表達(dá)和信號(hào)轉(zhuǎn)導(dǎo)蛋白和轉(zhuǎn)錄活化蛋白5b(signal transducer and activator of transcription 5b，STAT5b)中第699位酪氨酸的磷酸化水平。放射免疫分析法(radio immune assay，RIA)檢測(cè)IGF-1和GH的水平，逆轉(zhuǎn)錄-聚合酶鏈?zhǔn)椒磻?yīng)分析(reverse transcription-polymerase chain reaction analysis，RT-PCR)檢測(cè)豬工作組簇3抗原(swine workshop cluster 3 antigen，，SWC3 antigen)的水平。血漿葡萄糖的檢測(cè)采用葡萄糖氧化酶-4-氨基安替比林法。采用小分子化合物AG490作為JAK2信號(hào)通路的阻斷劑。 細(xì)胞實(shí)驗(yàn)： 1．觀察NO-1886對(duì)CYP7A1表達(dá)的影響：包括時(shí)間及劑量效應(yīng)；對(duì)GH的依賴性；對(duì)JAK2／STAT信號(hào)系統(tǒng)的依賴性；觀察NO-1886對(duì)GH信號(hào)通路中負(fù)向調(diào)控因子SIRPα1的影響； 2．觀察NO-1886對(duì)IGF-1的影響：檢測(cè)細(xì)胞內(nèi)及細(xì)胞外IGF-1的水平以及該變化對(duì)
[Abstract]:Objective: lipoprotein lipase lipase activator NO-1886 can down-regulate lipid in plasma. Glucose and insulin sensitivity can improve type 2 diabetes induced by diet. However, the specific mechanism of drug action is not clear. The aim of this study was to investigate the effect of this compound on growth hormone (GH) at cellular and global levels. Growth hormone. GH) signaling pathway insulin-like growth factor-1 like growth factor-1. The effects of IGF-1 and cholesterol 7 偽 hydroxylase cholesterol 7 偽 hydroxylase CYP7A1) were studied and its possible mechanism was discussed. Methods: human hepatoma blastoma G2 cells was used in human liver embryo G2 cell line. HepG2 cells and Guangxi Bama minipigs) human liver cells and animal models. CYP7A1 was detected by immunoblotting. Signal regulated protein 偽 1 signaling regulatory protein 偽 1 sip 偽 1). Expression of 尾 -Actinin and signal Transduction protein and Transcriptional Activator protein 5b. Signal transducer and activator of transcription 5b. The level of tyrosine phosphorylation at position 699 in STAT5b was detected by radioimmunoassay (RIA) and the levels of IGF-1 and GH were detected by radioimmunoassay (RIA). Reverse transcription-polymerase chain reaction (. Reverse transcription-polymerase chain reaction analysis. RT-PCR was used to detect swine workshop cluster 3 antigen. SWC3 antigenin. The level of plasma glucose was determined by glucose oxidase-4-aminoantipyrine method. The small molecular compound AG490 was used as a blocker for JAK2 signaling pathway. Cell experiments: 1. To observe the effect of NO-1886 on the expression of CYP7A1, including time and dose effect; Dependence on GH; Dependence on JAK2/STAT signal system; To observe the effect of NO-1886 on the negative regulatory factor SIRP 偽 1 in GH signaling pathway. 2. Observe the effect of NO-1886 on IGF-1: detect the level of intracellular and extracellular IGF-1 and its effect on
【學(xué)位授予單位】：南華大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2006
【分類號(hào)】：R363

【共引文獻(xiàn)】

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2 康斌;SIRP α及Gankyrin在神經(jīng)發(fā)育和分化中的表達(dá)調(diào)控和作用研究[D];第二軍醫(yī)大學(xué);2004年

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本文編號(hào)：1472435