NO-1886增敏生长激素信号通路提高胆固醇7α羟化酶和胰岛素样生长因子-1的表达

发布时间：2018-01-29 03:49

本文关键词： NO-1886 胆固醇7α羟化酶生长激素胰岛素样生长因子-1 信号调节蛋白α1　出处：《南华大学》2006年硕士论文　论文类型：学位论文

【摘要】：目的：脂蛋白酯酶(lipoprotein lipase，LPL)活化剂NO-1886能够通过下调血浆中脂质、葡萄糖及提高胰岛素敏感性而改善饮食诱导的2型糖尿病。但是具体的药物作用机制目前并不清楚。本实验旨在细胞及整体水平上探讨该化合物对生长激素(growth hormone，GH)信号通路中胰岛素样生长因子-1(insulin like growth factor-1，IGF-1)和胆固醇7α羟化酶(cholesterol 7α hydroxylase，CYP7A1)的作用，并初步探讨其可能的作用机制。方法：分别以人肝胚G2细胞株(human hepatoma blastoma G2 cells，HepG2 cells)和广西巴马小型猪(Guangxi Bama minipigs)为人肝脏细胞和动物模型，采用免疫印迹法(immuno-blotting)检测CYP7A1、信号调节蛋白α1(signaling regulatory protein α1，SIRPα1)、β-肌动蛋白(β-actin)的表达和信号转导蛋白和转录活化蛋白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)检测IGF-1和GH的水平，逆转录-聚合酶链式反应分析(reverse transcription-polymerase chain reaction analysis，RT-PCR)检测猪工作组簇3抗原(swine workshop cluster 3 antigen，，SWC3 antigen)的水平。血浆葡萄糖的检测采用葡萄糖氧化酶-4-氨基安替比林法。采用小分子化合物AG490作为JAK2信号通路的阻断剂。细胞实验： 1．观察NO-1886对CYP7A1表达的影响：包括时间及剂量效应；对GH的依赖性；对JAK2／STAT信号系统的依赖性；观察NO-1886对GH信号通路中负向调控因子SIRPα1的影响； 2．观察NO-1886对IGF-1的影响：检测细胞内及细胞外IGF-1的水平以及该变化对
[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 伪 hydroxylase cholesterol 7 伪 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 伪 1 signaling regulatory protein 伪 1 sip 伪 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 伪 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
【学位授予单位】：南华大学
【学位级别】：硕士
【学位授予年份】：2006
【分类号】：R363

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