| Abstract | 第5-7页 |
| 中文摘要 | 第8-10页 |
| Abbreviations/Acronyms | 第10-12页 |
| Chapter Ⅰ: A brief review: The molecular mechanism of regulating skeletal musclemitochondrial metabolism and fiber type switching | 第12-52页 |
| 1. Fiber type switching and mitochondrial metabolism in skeletal muscle | 第13-36页 |
| 1.1 The role of nuclear receptors and PGC-lα in regulating skeletal muscle fibertype conversion and energy metabolism | 第13-19页 |
| 1.2 The role of AMPK in regulating skeletal muscle fiber type conversion and energy metabolism | 第19-26页 |
| 1.3 Reference | 第26-36页 |
| 2. microRNA actions in skeletal muscle | 第36-52页 |
| 2.1 microRNA biogenesis | 第36-37页 |
| 2.2 microRNA mediated gene silencing | 第37-40页 |
| 2.3 microRNA actions in skeletal muscle | 第40-45页 |
| 2.4 Reference | 第45-52页 |
| Chapter Ⅱ: microRNA-499 couples mitochondrial metabolism to muscle fiber typeand ameliorates Duchenne muscular dystrophy | 第52-96页 |
| 1. Summary | 第53-54页 |
| 2. Introduction | 第54-56页 |
| 3. Materials and methods | 第56-63页 |
| 3.1 Animal studies | 第56页 |
| 3.2 Isolation of primary skeletal muscle cells and culture | 第56-57页 |
| 3.3 Skeletal muscle mitochondrial respiration studies | 第57-58页 |
| 3.4 Mitochondria oxygen consumption rate | 第58页 |
| 3.5 Cellular oxygen consumption measuremments | 第58-59页 |
| 3.6 Exercise studies | 第59页 |
| 3.7 Histological analyses | 第59-60页 |
| 3.8 Serum creatine kinase assay | 第60页 |
| 3.9 Gene expression array studies | 第60-61页 |
| 3.10 RNA analyses | 第61页 |
| 3.11 TaqMan miRNA | 第61页 |
| 3.12 Antibodies and immunoblotting studies | 第61-62页 |
| 3.13 LDH isoenzyme analysis | 第62页 |
| 3.14 RNAi experiments | 第62-63页 |
| 3.15 Cell transfection and luciferase reporter assays | 第63页 |
| 3.16 Study design and statistical analyses | 第63页 |
| 4. Results | 第63-87页 |
| 4.1 Dynamic changes of miR-499 and miR-208b parallels mitochondrial functionduring skeletal muscle fiber transformation | 第63-65页 |
| 4.2 MCK-miR-499 muscle is reprogrammed for increased capacity formitochondrial oxidation | 第65-68页 |
| 4.3 miR-499 promotes muscle mitochondrial oxidative capacity through PGC-1α | 第68-72页 |
| 4.4 miR-499 targets Fnip1,an AMPK interacting protein | 第72-73页 |
| 4.5 Fnip1/AMPK circuit regulates PGC-la signaling and mitochondrial function | 第73-76页 |
| 4.6 miR-499 is downregulated in muscular dystrophy model of mdx mice | 第76-77页 |
| 4.7 Restoration the expression of miR-499 ameliorates muscular dystrophy inmdx mice | 第77-82页 |
| 4.8 A model for the adaptive mitochondrial function during muscle fiber typetransformation | 第82-83页 |
| 4.9 Generation of Fnipl KO mice | 第83-85页 |
| 4.10 Loss of Fnipl increases the proportion of slow-oxidative muscle fibers andenhances mitochondria function in skeletal muscle | 第85-87页 |
| 5. Discussion | 第87-92页 |
| 6. Reference | 第92-96页 |
| Appendix | 第96-98页 |
| 致谢 | 第98-101页 |
| Publication | 第101-102页 |
