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关于P450酶在骨生物学及乳腺癌中作用的研究

发布时间:2021-07-12 22:17
  细胞色素P450酶(CYP)是一大类含有血红素分子的单加氧酶超家族,因其还原态与一氧化碳(CO)作用后,形成的复合物在450nm波长处会产生特异吸收峰而得名。在人体内,P450酶可以催化多种内源性物质(如性激素、糖皮质激素、胆固等)和外源性物质(如药物、毒物、前致癌物等)的I相代谢反应,包括羟基化,N-,O-和S-脱烷基化,磺化氧化,环氧化,脱氨,脱卤,过氧化和N-氧化还原,将亲脂性化合物转化为更亲水的代谢物。在人体中,已经发现了57种功能性P450酶。其中,大多数的人类P450酶,例如CYP1A2,CYP2B6,CYP2A6,CYP2C8,CYP2C9,CYP19,CYP2E1,CYP2D6和CYP3A4主要位于肝脏,并因其在药物代谢中的重要性已被进行广泛而深入的研究。然而,P450酶在肝脏以外人体器官中的研究则十分有限。细胞色素P450还原酶(CPR或POR)是微粒体中P450酶的主要电子供体。有研究表明,在POR敲除的小鼠模型中,骨骼中POR的缺失会导致颅骨发育缺陷和长骨中小梁骨密度降低。这表明了POR/CYP系统在骨骼的生长和发育中有着非常重要的意义。许多P450酶的代谢物都对... 

【文章来源】:天津大学天津市 211工程院校 985工程院校 教育部直属院校

【文章页数】:77 页

【学位级别】:硕士

【文章目录】:
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



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