| Abstract | 第5-8页 |
| 摘要 | 第9-16页 |
| 1. INTRODUCTION | 第16-40页 |
| 1.1 Background | 第16页 |
| 1.2 Expression of Radiation-Induced Effects in Biological Systems | 第16-18页 |
| 1.3 Bystander effects of radiation: a new paradigm | 第18-21页 |
| 1.4 Defining indirect effects of Radiation | 第21-22页 |
| 1.5 Type of radiations and its indirect effects | 第22-23页 |
| 1.6 Classical Experimental Approaches for studying Bystander Effects of radiation | 第23-25页 |
| 1.7 Mechanisms of radiation-induced bystander effects | 第25-27页 |
| 1.8 Apoptotic signaling pathway | 第27-31页 |
| 1.9 Role of indirect effect of radiation in neurodegenera | 第31-34页 |
| 1.10 Neuroprotection provided by glial cells against bystander effects of radiation | 第34-36页 |
| 1.11 Cell Signaling and secretome study | 第36-39页 |
| 1.12 Objectives | 第39-40页 |
| 2. MATERIALS AND METHODS | 第40-56页 |
| 2.1 Cell Line and Culture Conditions | 第40页 |
| 2.2 Irradiation and Irradiated Cell-Conditioned Medium (ICCM) | 第40-41页 |
| 2.3 Colony-Forming Assay | 第41-42页 |
| 2.4 Cell co-culture model in the transwell system | 第42页 |
| 2.5 Annexin V Assay | 第42页 |
| 2.6 TUNEL Assay | 第42-43页 |
| 2.7 Enzyme-linked Immunosorbent assay | 第43-44页 |
| 2.8 Cell viability assay by MTS method | 第44-45页 |
| 2.9 Estimation of cell number | 第45页 |
| 2.10 TUNEL assay | 第45-46页 |
| 2.11 Mitochondrial membrane potentials assay | 第46-47页 |
| 2.12 Analysis of cell cycle progression | 第47页 |
| 2.13 Caspase activity assays | 第47页 |
| 2.14 Quantitative real-time PCR | 第47-48页 |
| 2.15 Cell Culture for proteomic analysis | 第48-50页 |
| 2.16 Conditioned Media Sample Preparation and Trypsin Digestion | 第50-51页 |
| 2.17 Digestion, labeling, and desalting | 第51-52页 |
| 2.18 2D LC-MS/MS analysis | 第52-53页 |
| 2.19 Data analysis | 第53-54页 |
| 2.20 Western Blot Analysis | 第54-55页 |
| 2.21 Statistics Analysis | 第55-56页 |
| 3. RESULTS | 第56-86页 |
| 3.1 ICCM Induces dose and Time Dependent Neuronal cell death | 第56-59页 |
| 3.2 ICCM Induces Apoptosis in Neuronal SH-SY5Y Cell | 第59-60页 |
| 3.3 ICCM Elevates Cytokines Level and Oxidative Stress in Neuronal SH-SY5Y Cell | 第60-63页 |
| 3.4 ICCM Up-Regulate Key Apoptotic Protein Expression in Neuronal SH-SY5Y Cells | 第63-65页 |
| 3.5 Glial U87 cells showed resistance to ICCM exposure | 第65-66页 |
| 3.6 Coculture with glial U87 reduces the ICCM induce neuronal cells dea | 第66-68页 |
| 3.7 Glial U87 cells relieve neuronal SH-SY5Y from ICCM-induced apoptosis | 第68-69页 |
| 3.8 Glial U87 cells relieve neuronal SH-SY5Y cells from ICCM-induced mitochondrial depolarization in co-culture system | 第69-71页 |
| 3.9 Glial U87 cells protect neuronal SH-SY5Y cells from ICCM-induced oxidative stress by increasing the level of SOD | 第71-73页 |
| 3.10 Glial U87 relieved ICCM induced cell cycle arrest at S-phase and inhibit the expression of p53 in neuronal SH-SY5Y | 第73-75页 |
| 3.11 Coculture with glial U87 reduces the ICCM induced m RNA level of Fas receptor and inhibit the caspase-8 and caspase-3 activity in neuronal SH-SY5Y cell | 第75-77页 |
| 3.12 Co-culture with glial U87 cells decreases the expression of ICCM-induced apoptotic proteins in SH-SY5Y cells | 第77-79页 |
| 3.13 Coculture with glial U87 inhibited the expression of ICCM induced key apoptotic protein in neuronal SH-SY5Y cells | 第79-80页 |
| 3.14 BDNF and GDNF level was increased after coculture | 第80-82页 |
| 3.15 Cell Culture Optimization for proteomic analysis | 第82页 |
| 3.16 Proteins Identified by Mass Spectrometry | 第82-86页 |
| 4. DISSCUSION | 第86-104页 |
| 4.1 Bystander effect of radiation and neurotoxicity | 第86-89页 |
| 4.2 Glial U87 cells protect neuronal SH-SY5Y cells from indirect effect of radiation by reducing oxidative stress and apoptosis | 第89-93页 |
| 4.3 Astroglial U87 cells protect neuronal SH-SY5Y cells from indirect effect of radiation by reducing DNA damage and inhibiting Fas mediated apoptotic pathway in coculture system | 第93-99页 |
| 4.4 Proteomic analysis of ICCM | 第99-104页 |
| Coclusive remarls and future direction | 第104-106页 |
| References | 第106-124页 |
| Acknowledgement | 第124-125页 |
| Publications | 第125页 |
