在當今社會,隨著奶牛對代謝性、感染性和炎性疾病易感性的增加,奶牛養(yǎng)殖業(yè)承受著巨大的壓力。乳腺炎仍然是奶牛在泌乳期最常見的炎性疾病,導致乳汁產(chǎn)量減少、品質下降、治療費用增加。據(jù)統(tǒng)計,乳腺炎每年造成的經(jīng)濟損失在美國約為18億美元,在中國約為150—450億人民幣。金黃色葡萄球菌（S.aureus）是最常見和最具感染性的致病菌,可導致危及人類和動物生命的并發(fā)癥。反芻動物是致病性金黃色葡萄球菌最重要的宿主之一,奶牛是重要的反芻動物同時也是人類重要的食用動物�？股厥桥R床上治療金黃色葡萄球菌性乳腺炎的主要藥物,但在治療過程中產(chǎn)生的抗生素殘留及耐藥菌又會引發(fā)嚴重的食品安全和公共衛(wèi)生問題,現(xiàn)在許多國家已被禁止使用。因此,獸醫(yī)臨床實際迫切需要科學有效的防治乳腺炎的藥物。中藥（Tradition Chinese Medicines TCM）對于細菌性炎性疾病具有良好的治療效果,在食用動物行業(yè)有著廣闊的應用前景。本研究目的是闡明常春藤苷-C抑制TLRs-mediated介導的潛在奶牛乳腺炎炎性反應的調(diào)節(jié)通路及其作用機制,為臨床治療奶牛乳腺炎提供科學依據(jù)。1.奶牛乳腺炎臨床病理及炎癥因子分析乳腺炎是指乳腺組... 

【文章來源】：華中農(nóng)業(yè)大學湖北省 211工程院校 教育部直屬院校

【文章頁數(shù)】：163 頁

【學位級別】：博士

【文章目錄】：
摘要
Abstract
Abbreviations
Chapter 1 Introduction
    1.1 Mastitis in Dairy Cows
        1.1.1 General Aspects of Bovine Mastitis
        1.1.2 Classification of Mastitis
        1.1.3 Economic Implications of Mastitis
        1.1.4 Epidemiological Percept of Mastitis
        1.1.5 Factors Involved in Occurrence and Pathogenesis of Mastitis
            1.1.5.1 Host Factors
            1.1.5.2 Environmental Factors
            1.1.5.3 Pathogens
        1.1.6 Clinical Signs and Symptoms of Mastitis
        1.1.7 Diagnosis of Mastitis
        1.1.8 Strategies for Treatment of Mastitis
            1.1.8.1 Genetic Selection of Mastitis Resistance Cows
            1.1.8.2 Vaccination
            1.1.8.3 Bacteriophage Therapy
            1.1.8.4 Lactational Therapy
            1.1.8.5 Dry Cow Therapy
            1.1.8.6 Use of Teat Sealer
            1.1.8.7 Synthetic Drugs (Antibiotics) Should Be Used Carefully
            1.1.8.8 Natural Drugs Therapy
    1.2 Hederacoside-C to Treat Infectious Diseases
        1.2.1 Traditional Chinese Medicines (TCM) to Treat Infections
        1.2.2 Effective Ingredients and Therapeutic Effects of Hedera helix Compounds
        1.2.3 Hederacoside-C (HDC) and Its Anti-Inflammatory Effects and Mechanisms
    1.3 Immune Response in Mastitis
        1.3.1 Innate and Acquired Immunity
        1.3.2 Mastitis and Immunity Are Interlinked
        1.3.3 Defensive Mechanisms Due to Anatomical Structure
        1.3.4 Defensive Mechanisms at Cellular Levels
            1.3.4.1 Role of Neutrophils
            1.3.4.2 Role of Macrophages
            1.3.4.3 Role of Lymphocytes
        1.3.5 Endogenous Soluble Defensive Mechanism
    1.4 Inflammatory Responsive Mediators and Mechanisms in Mastitis
        1.4.1 Myeloperoxidase (MPO),A Novel Biomarker for Early Diagnosis
        1.4.2 Pattern Recognition Receptors (PRRs)
            1.4.2.1 Toll-Like Receptor 2 (TLR2)
            1.4.2.2 Toll-Like Receptor 4 (TLR4)
        1.4.3 Mitogen-Activated Protein Kinases (MAPKs)
            1.4.3.1 p38 MAPK
            1.4.3.2 Extracellular Signal Regulated Kinases (ERKs)
            1.4.3.3 The c-Jun Amino-terminal Kinases(JNKs)
        1.4.4 Nuclear Factor-Kappa B (NF-κB)
            1.4.4.1 NF-κB p-65
            1.4.4.2 Inhibitor of nuclear factor Kappa-B subunit alpha (IκBα)
        1.4.5 Cytokines,the Immune Modulators that Link Cellular Physiology withPathology
            1.4.5.1 Pro-inflammatory Cytokines
            1.4.5.2 Anti-inflammatory Cytokine
    1.5 Objectives and Significance
        1.5.1 Statement of Problem
        1.5.2 Aims
        1.5.3 Project Benefits and Outcomes
Chapter 2 Clinical Histopathology and Inflammatory Factors in Mastitis of DairyCows
    2.1 Objectives
    2.2 Methodology
        2.2.1 Chemicals and Reagents
        2.2.2 Target Animals (Cows) and Mammary Gland Tissue Sample Collection
        2.2.3 Histopathology
        2.2.4 Experimental Groups
        2.2.5 Isolation and Identification of S. aureus from Mammary Gland Tissues
        2.2.6 Western Blot Analysis for TLRs,NF-κB and MAPKs Proteins
        2.2.7 Real-Time Quantitative Polymerase Chain Reaction for Pro-InflammatoryCytokines
        2.2.8 Statistical Analysis
    2.3 Results
        2.3.1 Histopathological Evaluation of Mammary Glands
        2.3.2 S. aureus Characterization and Identification
        2.3.3 Expressions of TLR2 and TLR4 in Mammary Glands
        2.3.4 Phosphorylation of p-38,ERK and JNK in Mammary Glands
        2.3.5 Phosphorylation of p-65 and IκBα in Mammary Glands
        2.3.6 mRNA Expression Levels of TNF-α, IL-1β and IL-6 in Mammary Glands
    2.4 Discussion
Chapter 3 Hederacoside-C Inhibiting Inflammatory Response via TLR2 & TLR4and Their Downstream Signalling NF-κB & MAPKs Pathways in-vitro
    3.1 Objectives
    3.2 Materials and Methods
        3.2.1 Chemicals and Reagents
        3.2.2 The Multiplication and Growth of Staphylococcus aureus
        3.2.3 High Performance Liquid Chromatography
        3.2.4 Cell Viability Assay
        3.2.5 Cell Culturing and Treatment Groups
        3.2.6 Enzyme-Linked Immunosorbent Assay (ELISA)
        3.2.7 Real-Time Quantitative Polymerase Chain Reaction
        3.2.8 Western Blot Analysis
        3.2.9 Statistics
    3.3 Results
        3.3.1 Purity of HDC and S. aureus Growth upon HDC Administration
        3.3.2 Effect of HDC on RAW 264.7 Cell Viability
        3.3.3 HDC modulates Protein/Gene Expression Levels of Inflammatory Cytokinein S. aureus-induced Inflammatory RAW 264.7 cells
        3.3.4 HDC inhibits TLR2 & TLR4 Expressions in S. aureus-inducedInflammation RAW 264.7 cells
        3.3.5 HDC attenuates NF-κB cascade in S. aureus-induced Inflammation RAW264.7 cells
        3.3.6 HDC attenuates MAPKs cascade in S. aureus-induced Inflammation RAW264.7 cells
    3.4 Discussion
Chapter 4 Hederacoside-C Suppressing Inflammatory Response in Mastitis viaInhibiting TLR2 & TLR4 and Their Downstream Signalling NF-κB & MAPKsPathways in-vivo
    4.1 Objectives
    4.2 Materials and Methods
        4.2.1 Chemicals and Reagents
        4.2.2 Selection of Experimental Animals and Treatment Groups
        4.2.3 Histopathological Evaluation
        4.2.4 Measurement of Myeloperoxidase (MPO) in the Mammary Glands
        4.2.5 Enzyme-Linked Immunosorbent Assay (ELISA)
        4.2.6 Real-Time Quantitative Polymerase Chain Reaction (qRT-PCR)
        4.2.7 Analysis by Western Blotting
        4.2.8 Statistical Analysis
    4.3 Results
        4.3.1 Histopathological Changes and Analysis of Mammary Glands
        4.3.2 Effects of HDC on the Myeloperoxidase Activity
        4.3.3 Effects of HDC on the Inflammatory Cytokines in S. aureus-inducedMastitis
        4.3.4 Effects of HDC on TLR2 & TLR4 Expression in S. aureus-induced Mastitis
        4.3.5 HDC Suppresses the NF-κB Pathway in S. aureus-induced Mastitis
        4.3.6 HDC Suppresses the MAPKs pathway in S. aureus-induced Mastitis
    4.4 Discussion
Chapter 5 Discussion and Conclusion
    Discussion
    Conclusion
    Achieved Goals
    Future Suggestions
References
List of Figures
List of Tables
Acknowledgement
Appendix Ⅰ Publication List and Related Research
    Publications List
    Related Research


【參考文獻】：
期刊論文
[1]The Immune System, Cytokines, and Biomarkers in Autism Spectrum Disorder[J]. Anne Masi,Nicholas Glozier,Russell Dale,Adam J.Guastella.  Neuroscience Bulletin. 2017(02)



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