細胞色素P450酶（CYP）是一大類含有血紅素分子的單加氧酶超家族,因其還原態(tài)與一氧化碳（CO）作用后,形成的復(fù)合物在450nm波長處會產(chǎn)生特異吸收峰而得名。在人體內(nèi),P450酶可以催化多種內(nèi)源性物質(zhì)（如性激素、糖皮質(zhì)激素、膽固等）和外源性物質(zhì)（如藥物、毒物、前致癌物等）的I相代謝反應(yīng),包括羥基化,N-,O-和S-脫烷基化,磺化氧化,環(huán)氧化,脫氨,脫鹵,過氧化和N-氧化還原,將親脂性化合物轉(zhuǎn)化為更親水的代謝物。在人體中,已經(jīng)發(fā)現(xiàn)了57種功能性P450酶。其中,大多數(shù)的人類P450酶,例如CYP1A2,CYP2B6,CYP2A6,CYP2C8,CYP2C9,CYP19,CYP2E1,CYP2D6和CYP3A4主要位于肝臟,并因其在藥物代謝中的重要性已被進行廣泛而深入的研究。然而,P450酶在肝臟以外人體器官中的研究則十分有限。細胞色素P450還原酶（CPR或POR）是微粒體中P450酶的主要電子供體。有研究表明,在POR敲除的小鼠模型中,骨骼中POR的缺失會導(dǎo)致顱骨發(fā)育缺陷和長骨中小梁骨密度降低。這表明了POR/CYP系統(tǒng)在骨骼的生長和發(fā)育中有著非常重要的意義。許多P450酶的代謝物都對... 

【文章來源】：天津大學天津市 211工程院校 985工程院校 教育部直屬院校

【文章頁數(shù)】：77 頁

【學位級別】：碩士

【文章目錄】：
摘要
Abstract
Chapter 1 Introduction
    1.1 Cytochrome P450s and Their Possible Role in Bone Biology
        1.1.1 Introduction of Cytochrome P450s
        1.1.2 The Role of CYPs in Bone Biology
    1.2 CYPs and Inflammation-Induced Osteoporosis
        1.2.1 Bone Remodeling
        1.2.2 CYPs Involved Bone Biology and Inflammation-induced Osteoporosis
    1.3 Crosstalk between Metastatic Breast Cancer and Bone Microenvironment
        1.3.1 Breast Cancer
        1.3.2 Bone Metastases
        1.3.3 Mechanisms of Osteolytic Metastasis
Chapter 2 Materials and Methods
    2.1 Materials and Reagents
    2.2 Instruments and Consumables
    2.3 Methods
        2.3.1 Cell Culture
        2.3.2 RNA Extraction and Reverse Transcription
        2.3.3 Quantitative Real-time PCR Analysis
        2.3.4 Statistical analysis
        2.3.5 Detailed Experimental Design
Chapter 3 Results
    3.1 Comparison of Cytochrome P450 Expression in Four Different HumanOsteoblast Models
    3.2 Cytochrome P450 Expression Pattern in Human Osteoblast duringOsteogenic Differentiation with or without TNF-α Treatment
        3.2.1 CYPs Gene Expression Pattern in MG63 and HOB during Different Stages ofOsteogenic Differentiation
        3.2.2 Effects of TNF-α on CYPs Gene Expression in MG63 and HOB
    3.3 The Role of CYPs in the Crosstalk Interaction between Human Osteoblastand Breast Cancer Cells
        3.3.1 MG63 Cells and HOB Cells Cultured in MCF-7 Conditioned Medium
        3.3.2 MCF-7 Cells Cultured in HOB Conditioned Medium
Chapter 4 Discussions
    4.1 Comparison of Cytochrome P450 Expression in Four Different HumanOsteoblast Models
    4.2 Cytochrome P450 Expression Pattern in Human Osteoblast duringOsteogenic Differentiation with or without TNF-α Treatment
        4.2.1 CYPs Gene Expression Pattern in MG63 and HOB during Different Stages ofOsteogenic Differentiation
        4.2.2 Effects of TNFα on CYPs Gene Expression in MG63 and HOB
        4.2.3 Time Dependent Influence of TNF-α on CYPs Expression
    4.3 The Role of CYPs in the Crosstalk Interaction between Human Osteoblastand Breast Cancer Cells
        4.3.1 MG63 Cells and HOB Cells-MCF-7 Conditioned Medium
        4.3.2 MCF-7 Cells-HOB Conditioned Medium
Chapter 5 Conclusions and Future Prospects
    5.1 Comparison of Cytochrome P450 Expression in Four Different HumanOsteoblast Models
    5.2 Cytochrome P450 Expression Pattern in Human Osteoblast duringOsteogenic Differentiation with or without TNF-α Treatment
    5.3.The Role of CYPs in the Crosstalk Interaction between Human Osteoblastand Breast Cancer Cells
References
Notes on Publications and Participation in Scientific Research
Acknowledgement



本文編號：3280762