| ABSTRACT | 第3-4页 |
| 摘要 | 第5-10页 |
| ABBREVIATIONS | 第10-15页 |
| Chapter 1 Introduction | 第15-23页 |
| 1.1 Bile acid | 第15-20页 |
| 1.1.1 Bile acid synthesis | 第15-16页 |
| 1.1.2 The enterohepatic circulation of bile acids | 第16-18页 |
| 1.1.3 Bile acid signaling pathway in liver and intestine | 第18-19页 |
| 1.1.4 Bile acid quantification | 第19-20页 |
| 1.2 Diabetic encephalopathy | 第20-21页 |
| 1.2.1 Research progress on diabetic encephalopathy | 第20页 |
| 1.2.2 Diabetes and bile acid | 第20-21页 |
| 1.3 The vagal nerve system | 第21-23页 |
| Chapter 2 The establishment of a UPLC-MS method for bile acid quantification | 第23-37页 |
| 2.1 Material | 第23-24页 |
| 2.1.1 Reagent | 第23页 |
| 2.1.2 Equipment | 第23-24页 |
| 2.2 Experimental method | 第24-27页 |
| 2.2.1 Preparation of standard solutions | 第24-26页 |
| 2.2.2 Collection and storage of biosamples | 第26页 |
| 2.2.3 Sample preparation | 第26页 |
| 2.2.4 Chromatographic and mass spectrometric conditions | 第26-27页 |
| 2.3 Method validation | 第27-28页 |
| 2.3.1 Linearity, LOD and LOQ | 第27页 |
| 2.3.2 Precision and accuracy | 第27-28页 |
| 2.3.3 Stability | 第28页 |
| 2.3.4 Recovery | 第28页 |
| 2.3.5 Matrix effect | 第28页 |
| 2.4 Results and discussion | 第28-36页 |
| 2.4.1 Method development and optimization | 第28-30页 |
| 2.4.2 Method validation | 第30-36页 |
| 2.5 Summary | 第36-37页 |
| Chapter 3 Bile acid metabolism and signaling pathway in diabetic encephalopathy | 第37-61页 |
| 3.1 Material | 第37页 |
| 3.1.1 Chemical and reagents | 第37页 |
| 3.1.2 Equipment | 第37页 |
| 3.2 Experimental method | 第37-43页 |
| 3.2.1 Diabetic encephalopathy model establishment | 第37-39页 |
| 3.2.2 Morris water maze test | 第39页 |
| 3.2.3 Bile acid extraction | 第39-40页 |
| 3.2.4 Bacterial DNA extraction | 第40页 |
| 3.2.5 Bacterial quantification | 第40-41页 |
| 3.2.6 RNA extraction and Quantitative RT-PCR | 第41-42页 |
| 3.2.7 Western Blot | 第42-43页 |
| 3.2.8 Biochemical assay | 第43页 |
| 3.2.9 Statistical analysis | 第43页 |
| 3.3 Results | 第43-56页 |
| 3.3.1 The blood glucose concentrations and Morris water maze test | 第43-46页 |
| 3.3.2 The bile acid metabolism and signaling | 第46-56页 |
| 3.4 Discussion | 第56-60页 |
| 3.5 Summary | 第60-61页 |
| Chapter 4 Bile acid metabolism and signaling pathway in the vagotomy rats | 第61-77页 |
| 4.1 Material | 第61页 |
| 4.1.1 Chemical and reagents | 第61页 |
| 4.1.2 Equipment | 第61页 |
| 4.2 Experimental method | 第61-64页 |
| 4.2.1 Subdiaphragmatic vagotomy rat model establishment | 第61-62页 |
| 4.2.2 Quantitative RT-PCR | 第62-63页 |
| 4.2.3 Western blot | 第63-64页 |
| 4.2.4 ALT | 第64页 |
| 4.2.5 Statistical analysis | 第64页 |
| 4.3 Results | 第64-73页 |
| 4.3.1 SDV decreased body weight gain and increased bile flow in rats | 第64-65页 |
| 4.3.2 SDV markedly increased the concentration of unconjugated BAs and the BA hydrophobicity index in the bile of rats | 第65-66页 |
| 4.3.3 SDV markedly increased the concentration of unconjugated BAs and glycine-conjugated BAs in the serum of rats | 第66-67页 |
| 4.3.4 SDV increased the hydrophobicity index of BAs without altering the concentration of total BAs in livers of rats | 第67-68页 |
| 4.3.5 SDV had little effect on hepatic BA transporters but decreased them RNA expression of Asbt in the ileum of rats | 第68-69页 |
| 4.3.6 SDV suppressed both the m RNA and protein expression of Cyp7a1,which was not due to activation of Fxr-Shp signaling in the liver | 第69-71页 |
| 4.3.7 SDV activated the Fxr-Fgf15 signaling in ileum of rats | 第71-72页 |
| 4.3.8 SDV suppressed the protein levels of Claudin-5 and Occludin in ileumof rats | 第72-73页 |
| 4.4 Discussion | 第73-75页 |
| 4.5 Summary | 第75-77页 |
| Chapter 5 Conclusion | 第77-79页 |
| Reference | 第79-93页 |
| Notes on publications and participation in scientific research | 第93-95页 |
| Acknowledgement | 第95页 |
