| 摘要 | 第9-11页 |
| ABSTRACT | 第11-13页 |
| CHAPTER 1 Introduction | 第15-28页 |
| 1.1 Endochodreal Ossification | 第15-16页 |
| 1.2 Epiphyseal plate or Growth plate | 第16-17页 |
| 1.3 Chicken Growth Plate | 第17-20页 |
| 1.4 Tibial Dyschondroplasia | 第20-22页 |
| 1.5 Heat Shock Protein 90 (Hsp90) | 第22-23页 |
| 1.6 Role of Hsp90 in Angiogenesis | 第23-24页 |
| 1.7 Discovery of Hsp90 inhibitors and Hsp90 inhibition in TD research | 第24-27页 |
| 1.7.1 Celastrol | 第25页 |
| 1.7.2 Gambogic Acid | 第25-26页 |
| 1.7.3 Novobiocin | 第26-27页 |
| 1.8 Conclusion and Hypothesis | 第27-28页 |
| CHAPTER 2 Hsp90 inhibitor celastrol reinstates growth plate angiogenesis in thiram-induced tibialdyschondroplasia | 第28-39页 |
| 2.1 Objectives | 第28页 |
| 2.2 Materials and Methods | 第28-31页 |
| 2.2.1 Experimental birds | 第28页 |
| 2.2.2 Celastrol preparation | 第28页 |
| 2.2.3 Establishment and treatment of thiram-induced TD | 第28-29页 |
| 2.2.4 Hematoxylin & Eosin (H&E) staining | 第29页 |
| 2.2.5 RNA extraction and reverse transcription | 第29页 |
| 2.2.6 Reverse transcription quantitative-real time PCR (RT-qPCR) | 第29-30页 |
| 2.2.7 Western blot analysis | 第30-31页 |
| 2.2.8 Statistical Analysis | 第31页 |
| 2.3 Results | 第31-36页 |
| 2.3.1 Effect of Celastrol on thiram-induced TD affected birds | 第31-33页 |
| 2.3.2 Morphometric analysis of growth plate | 第33-34页 |
| 2.3.3 Hsp90 level in TD affected growth plates correlated with the inhibitory effect ofcelastrol | 第34页 |
| 2.3.4 VEGF and Flk-1 receptor level in TD affected growth plates | 第34-36页 |
| 2.4 Discussion | 第36-39页 |
| CHAPTER 3 Hsp90 inhibitor celastrol attenuate liver damage caused by thiram | 第39-43页 |
| 3.1 Objectives | 第39页 |
| 3.2 Materials and Methods | 第39-40页 |
| 3.2.1 Animal selection & ethics | 第39页 |
| 3.2.2 Experimental design and induction of TD | 第39-40页 |
| 3.2.3 Blood serum biomarkers assay. | 第40页 |
| 3.2.4 Liver tissue sample collection and antioxidant determination | 第40页 |
| 3.2.5 Statistical analysis | 第40页 |
| 3.3 Results | 第40-41页 |
| 3.4 Discussion | 第41-43页 |
| CHAPTER 4 Gambogic Acid Inhibits Hsp90 Expressions and restored the growth plate width in Thiram-Induced Tibial Dyschondroplasia | 第43-50页 |
| 4.1Objectives | 第43页 |
| 4.2 Materials and Methods | 第43-45页 |
| 4.2.1 Animal welfare & ethics | 第43页 |
| 4.2.2 Experimental design and bird?s selection | 第43-44页 |
| 4.2.3 Birds slaughtering and sample collection | 第44页 |
| 4.2.4 Quantitave real time polymerase chain reaction | 第44页 |
| 4.2.5 Liver antioxidant enzyme sampling | 第44-45页 |
| 4.2.6 Statistical analysis | 第45页 |
| 4.3 Results | 第45-47页 |
| 4.3.1 Effects of Hsp90 inhibition on growth plate size with GA | 第45页 |
| 4.3.2 Hsp90 expressions before and after GA administration in thiram induced TD | 第45-46页 |
| 4.3.3 Liver antioxidant activities in thiram fed birds and gambogic acid treatment | 第46-47页 |
| 4.4 Discussion | 第47-50页 |
| CHAPTER 5 Novobiocin Ameliorate Tibial Dyschondroplasia through Inhibition of Hsp-90 Expressions inAvian Growth Plate | 第50-63页 |
| 5.1 Objectives | 第50页 |
| 5.2 Materials and Methods | 第50-52页 |
| 5.2.1 Animal ethics and welfare | 第50页 |
| 5.2.2 Induction and evaluation of disease | 第50页 |
| 5.2.3 Birds slaughtering and tissue extraction | 第50-51页 |
| 5.2.4 RNA extraction and reverse transcription | 第51页 |
| 5.2.5 Reverse transcription quantitative-real time PCR (RT-qPCR) | 第51页 |
| 5.2.6 Immunohistochemistry (IHC) and Hematoxylin & Eosin (H&E) staining | 第51-52页 |
| 5.2.7 Western blot analysis | 第52页 |
| 5.2.8 Statistical analysis | 第52页 |
| 5.3 Results | 第52-59页 |
| 5.3.1 Morphological examination of growth plate from TD affected and Novobiocintreated group | 第52-53页 |
| 5.3.2 Histological features of growth plate (GP) | 第53-55页 |
| 5.3.3 Inhibitory effect of Novobiocin on Hsp90 level in TD affected growth plates | 第55-57页 |
| 5.3.4 Immunohistochemical evaluation of epiphyseal growth plate | 第57-58页 |
| 5.3.5 Differential expression of proteoglycan aggrecan in growth plate | 第58-59页 |
| 5.4 Discussions | 第59-63页 |
| CHAPTER 6 | 第63-65页 |
| 6.1 Conclusion | 第63-64页 |
| 6.1.1 Study I | 第63页 |
| 6.1.2 Study II | 第63页 |
| 6.1.3 Study III | 第63-64页 |
| 6.1.4 Study IV | 第64页 |
| 6.2 Future Prospects | 第64-65页 |
| References | 第65-75页 |
| List of Figures | 第75-76页 |
| Lists of Tables | 第76-77页 |
| Acknowledgements | 第77-79页 |
| Appendix I | 第79-81页 |
| Publications | 第79-81页 |
