脛骨軟骨發(fā)育不良（Tibial dyschondroplasia,TD）是家禽較為常見的骨骼疾病,主要發(fā)生于快大型、速生長的肉雞、火雞等。TD主要病理學特征是病雞脛骨近干骺端干骺面生長板內出現(xiàn)無血管化、無鈣化的白色“軟骨栓”。該病主要引起腿部疾患,在商品肉雞中最為常見,嚴重降低肉的品質,造成巨大的經濟損失,目前該病已成為家禽跛足的主要原因,嚴重影響動物福利。1.基于HIF-1α/VEGF信號通路研究川芎嗪對脛骨軟骨發(fā)育不良的影響肉雞脛骨軟骨發(fā)育不良（TD）是許多禽類常見的骨骼疾病,其特征是生長板（GP）構建異常,導致GP內持續(xù)無血管、無鈣化病變。川芎嗪（TMP）被廣泛應用于神經血管疾病和肺動脈高壓的治療,但TMP對肉雞TD的是否具有一定的治療作用,尚未見報道。因此,本研究隨機選擇AA肉雞210只,飼喂標準日糧;于第三天隨機將其分為3組:對照組（n=70）給予標準日糧,福美雙組（n=70）和TMP組（n=70）從第4天至第7天,均以飼料添加福美雙（thiram,50mg/kg）誘導TD。第8天,TD組與對照組一樣給予標準日糧,TMP組給予TMP（30mg/kg/d）,直至試驗結束,分別于... 

【文章來源】：華中農業(yè)大學湖北省 211工程院校 教育部直屬院校

【文章頁數(shù)】：119 頁

【學位級別】：博士

【文章目錄】：
摘要
ABSTRACT
LIST OF ABBREVIATIONS
CHAPTER 1 General Introduction
    1.1 Endochondral bone formation and ossification
    1.2 Long bone growth and development
    1.3 Epiphyseal growth plate
        1.3.1 Reserve zone of GP
        1.3.2 Proliferative zone of GP
        1.3.3 Transition zone of GP
        1.3.4 Prehypertrophic zone of GP
        1.3.5 Hypertrophic zone of GP
    1.4 Avian growth plate
    1.5 Tibial dyschondroplasia
    1.6 Tetramethylthiuram disulfide (Thiram)
    1.7 TD and gene expression
    1.8 Role of hypoxia inducible factor-1α in TD
    1.9 Role of VEGF and VEGFR1 in TD
    1.10 Role of PI3K and Akt
    1.11 Role of Cyclooxygenase-2
    1.12 Role of integrin beta 3
    1.13 Prevention and treatment of TD
    1.14 Traditional Chinese medicines
        1.14.1 Tetramethylpyrazine
        1.14.2 Astragaloside IV
    1.15 Conclusion and hypothesis
CHAPTER 2 Effects of tetramethylpyrazine on tibial dyschondroplasia by regulating HIF-1α and VEGF
    2.1 Introduction
    2.2 Objectives
    2.3 Materials and Methods
        2.3.1 Animal ethics and welfare
        2.3.2 Chicken management and experimental design
        2.3.3 Morphological, production parameters analysis and sample collection
        2.3.4 Hematoxylin and eosin (H&E) staining
        2.3.5 Immunohistochemistry
        2.3.6 Quantitative-real time PCR (RT-qPCR)
        2.3.7 Western blot analysis
        2.3.8 Statistical analysis
    2.4 Results
        2.4.1 TMP prevented the mortality in chickens
        2.4.2 Performance parameters analysis of chickens
        2.4.3 Effect of TMP on TD score
        2.4.4 The overall tibial parameters analysis
        2.4.5 Clinical observation of thiram-induced TD and TMP chickens
        2.4.6 Histological examination of the tibial growth plates
        2.4.7 Immunohistochemistry of tibial growth plates
        2.4.8 The expression of HIF-1α/VEGF genes and proteins level in growth plate
        2.4.9 Overall effect of TMP on TD chickens
    2.5 Discussion
CHAPTER 3 Ligustrazine remodels the toxicity in thiram-induced tibial dyschondroplasia chickens: involvement of new molecules modulating integrin beta-3
    3.1 Introduction
    3.2 Objectives
    3.3 Materials and Methods
        3.3.1 Animal ethics
        3.3.2 Experimental design and treatment
        3.3.3 Incidence and severity of TD
        3.3.4 Serum analysis
        3.3.5 Measurement of liver antioxidant enzymes
        3.3.6 Hematoxylin & Eosin (H&E) and immunofluorescence staining
        3.3.7 Tibia index
        3.3.8 Quantitative real time polymerase chain reaction (RT-qPCR)
        3.3.9 Western blot analysis
        3.3.10 Statistical analysis
    3.4 Results
        3.4.1 Chickens performance
        3.4.2 Biochemical criterion analysis of serum
        3.4.3 Determination of oxidative stress in liver
        3.4.4 Tibia bone observation and H&E examination
        3.4.5 Incidence and severity of TD
        3.4.6 Tibial index
        3.4.7 Histopathology micrograph
        3.4.8 Expression of ITGB3
    3.5 Discussion
CHAPTER 4 Protective effect of astragaloside IV to inhibit tibial dyschondroplasia on vascular endothelial cell based PI3K/Akt/HIF-1α signaling
    4.1 Introduction
    4.2 Objectives
    4.3 Materials and Methods
        4.3.1 Ethics approval
        4.3.2 Chicken management and experimental design
        4.3.3 Production parameter analysis and sample collection
        4.3.4 Biochemical criterion determination
        4.3.5 Measurement of liver antioxidant enzymes
        4.3.6 Hematoxylin and Eosin (H&E) staining
        4.3.7 RT-qPCR assay
        4.3.8 Western blotting
        4.3.9 Immunohistochemistry assay
        4.3.10 Statistical analysis
    4.4 Results
        4.4.1 Production parameter analysis
        4.4.2 H&E staining
        4.4.3 Tibial parameters analysis
        4.4.4 Biochemical criterion determination
        4.4.5 Antioxidant ability of AST-IV
        4.4.6 Effect of AST-IV on overall performance of chickens
        4.4.7 RT-qPCR assay
        4.4.8 Western blotting analysis
        4.4.9 Immunohistochemistry analysis
        4.4.10 Astragaloside IV regulates PI3K/Akt/HIF-1α signaling pathway
    4.5 Discussion
CHAPTER 5 Conclusions and Future prospectus
    5.1 Conclusion
    5.2 Future prospectus
REFERENCES
Acknowledgement
Publications


【參考文獻】：
期刊論文
[1]黃芪皂苷對化療貧血小鼠PI3K/Akt/mTOR信號通路相關基因mRNA表達的影響[J]. 喬鐵,梁可,馬進,林蔗茹,鄭冰元,張立德.  中國中藥雜志. 2016(20)
[2]The role of vascular endothelial growth factor in ossification[J]. Ricky Wong,Alex Wenden,A Bakr M Rabie.  International Journal of Oral Science. 2012(02)



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