本文關鍵詞： NO-1886 膽固醇7α羥化酶 生長激素 胰島素樣生長因子-1 信號調節(jié)蛋白α1　出處：《南華大學》2006年碩士論文　論文類型：學位論文

【摘要】：目的：脂蛋白酯酶(lipoprotein lipase，LPL)活化劑NO-1886能夠通過下調血漿中脂質、葡萄糖及提高胰島素敏感性而改善飲食誘導的2型糖尿病。但是具體的藥物作用機制目前并不清楚。本實驗旨在細胞及整體水平上探討該化合物對生長激素(growth hormone，GH)信號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制。 方法：分別以人肝胚G2細胞株(human hepatoma blastoma G2 cells，HepG2 cells)和廣西巴馬小型豬(Guangxi Bama minipigs)為人肝臟細胞和動物模型，采用免疫印跡法(immuno-blotting)檢測CYP7A1、信號調節(jié)蛋白α1(signaling regulatory protein α1，SIRPα1)、β-肌動蛋白(β-actin)的表達和信號轉導蛋白和轉錄活化蛋白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IGF-1和GH的水平，逆轉錄-聚合酶鏈式反應分析(reverse transcription-polymerase chain reaction analysis，RT-PCR)檢測豬工作組簇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信號通路的阻斷劑。 細胞實驗： 1．觀察NO-1886對CYP7A1表達的影響：包括時間及劑量效應；對GH的依賴性；對JAK2／STAT信號系統(tǒng)的依賴性；觀察NO-1886對GH信號通路中負向調控因子SIRPα1的影響； 2．觀察NO-1886對IGF-1的影響：檢測細胞內及細胞外IGF-1的水平以及該變化對
[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
【學位授予單位】：南華大學
【學位級別】：碩士
【學位授予年份】：2006
【分類號】：R363

【共引文獻】

相關期刊論文 前2條

1 秦建民;王紅陽;吳孟超;;生物信號轉導異常在肝癌發(fā)生發(fā)展中的作用[J];世界華人消化雜志;2001年09期

2 單云峰,康斌,李寶安,鄢和新,周偉平,吳孟超,王紅陽;信號調節(jié)蛋白α1在肝細胞癌中的作用(英文)[J];The Chinese-German Journal of Clinical Oncology;2003年03期

相關博士學位論文 前2條

1 張朝云;黃芪多糖對糖尿病大鼠GH/IGF-Ⅰ軸的影響及其機制研究[D];復旦大學;2003年

2 康斌;SIRP α及Gankyrin在神經發(fā)育和分化中的表達調控和作用研究[D];第二軍醫(yī)大學;2004年

相關碩士學位論文 前2條

1 張陽;SPAP2在小鼠組織中的分布以及在Hela細胞中的表達[D];吉林大學;2006年

2 孫立文;3BP2多克隆抗體的制備及其與SHP-1之間的相互關系[D];吉林大學;2006年

本文編號：1472435