hsp90抑制剂对福美双诱导的胫骨软骨发育不良肉鸡生长板血管生成的影响临床兽医学专业论文.docxVIP

Effect Effect of Hsp90 inhibit凹s avian growth plate angiogenesis in thiram-induced nbial dyschondroplasla CoNTENTS 摘要 ．V ABSTRACT． ．．VⅡ ABBREVIATIONS ．．X CHAPTER 1 1 Introduction ．1 1．1 Endochodreal Ossification 1 1．2 Epiphyseal plate or Growth plate ．．2 1．3 Chicken Growth Plate ．3 1．4 Tibial Dyschondroplasia 6 1．5 Heat Shock Protein 90(Hsp90) ．8 1．6 Role oflisp90 in Angiogenesis ．9 1．7 Discovery oflisp90 inhibitors and Hsp90 inhibition in TD research ．10 1．7．1 Celastrol 11 1．7．2 Gambogic Acid 1 1 1．7．3 Novobiocin ．12 1．8 Conclusion and Hypothesis 13 CHAPTER 2 14 Hsp90 inhibitor celastrol reinstates growth plate angiogenesis in thiram-induced tibial dyschondroplasia 14 2．1 Objectives ．．14 2．2 Materials and Methods 14 2．2．1 Experimental birds ．14 2．2．2 Celastrol preparation．．． ．．．．．．． 14 2．2．3 Establishment and treatment ofthiram-induced TD ．14 2．2．4 HematoxylinEosin(HE)staining ．15 2．2．5 RNAextraction and reverse transcription ．．15 2．2．6 Reverse transcription quantitative-real time PCR(RT-qPCR) 1 5 I College ofVeterinary Medicine／Animal Science，Huazhong Agricultural University,Wuhan China,20 1 6 万方数据 Effect Effect of Hsp90 inhibitors avian growth plate angiogenesis in thiram-induced ri—b——ial dyschondr—o—plas—ia— 2．2．7 Western blot analysis 16 2．2．8 Statistical Analysis ．17 2．3 Results ．1 7 2．3．1 Efiect ofCelastrol on thiram．induced TD affected birds ．．17 2．3．2 Morphometric analysis ofgrowth plate ．．19 2．3．3 Hsp90 level in TD affected growth plates correlated with the inhibitory effect of celastrol 20 2．3．4 VEGF and Flk-1 receptor level in TD affected growth plates ．20 2．3．5Discussion 22 CHAPTER 3 ．．25 Hsp90 inhibitor celastrol attenuate liver damage caused by thiram．．． ．．25 3．1 Objectives ．．25 3．2 Materials and Methods ． ．．25 3．2．Animal selection 2女：ethics 25 3．2．2 Experimental design and induction ofTD ．25 3．2．3Blood serumbiomarkers assay ．26 3．2．4 Liver tissue sample collection and antioxidant determination 26 3．2．5 Statistical analysis 26 ：I．3 Results 26 3