| List of Tables | 第10-11页 |
| List of Figures | 第11-13页 |
| List of Abbreviations | 第13-15页 |
| 摘要 | 第15-18页 |
| General abstract | 第18-20页 |
| Introduction & Literature Review | 第22-33页 |
| 1 Chemical induced hepatotoxicity | 第22-30页 |
| 1.1 Liver and liver injury | 第22-24页 |
| 1.2 Experimental models of chemical induced hepatotoxicity | 第24-26页 |
| 1.3 Mechanisms of chemical induced hepatotoxicity | 第26-30页 |
| 2 Introduction to experimental work | 第30-33页 |
| 2.1 Rationale for study | 第30-32页 |
| 2.2 Hypothesis | 第32页 |
| 2.3 The objective of study | 第32-33页 |
| Chapter 1 Boschniakia rossica prevents the carbon tetrachloride induced hepatotoxicity in rat | 第33-54页 |
| Abstract | 第34-35页 |
| 1.1 Introduction | 第35-37页 |
| 1.2 Materials and Methods | 第37-41页 |
| 1.2.1 Preparation of the test substances | 第37页 |
| 1.2.2 Animals | 第37页 |
| 1.2.3 Experimental design | 第37-38页 |
| 1.2.4 Blood and liver sample preparation | 第38页 |
| 1.2.5 Serum marker enzymes,albumin and TNF-α assays | 第38页 |
| 1.2.6 Liver oxidative damage assay | 第38-39页 |
| 1.2.7 Hepatic antioxidative defense potentials | 第39页 |
| 1.2.8 Liver nitrite level | 第39页 |
| 1.2.9 Western blot analysis of hepatic iNOS,COX-2,HO-1 and CYP2E1 | 第39页 |
| 1.2.10 CYP2E1-specific monooxygenase activity | 第39-40页 |
| 1.2.11 Statistical analysis | 第40-41页 |
| 1.3 Results | 第41-50页 |
| 1.3.1 Eflect of BRE on serum ALT,AST, ALP and ALB | 第41页 |
| 1.3.2 Effect of BRE on serum TNF-α level | 第41页 |
| 1.3.3 Effect of BRE on hepatic oxidative damage | 第41页 |
| 1.3.4 Effect of BRE on hepatic antioxidative defense system | 第41-42页 |
| 1.3.5 Effect of BRE on hepatic nitrite level and iNOS protein expression | 第42页 |
| 1.3.6 Effect of BRE on hepatic COX-2 and HO-1 protein expression | 第42页 |
| 1.3.7 Effect of BRE on hepatic CYP2E1 protein expression and function | 第42-50页 |
| 1.4 Discussion | 第50-53页 |
| 1.5 Conclusion | 第53-54页 |
| Chapter 2 Hepatoprotective effect of polysaccharides from Boschniakia rossica on carbon tetrachloride-induced toxicity in mice | 第54-82页 |
| Abstract | 第55-56页 |
| 2.1 Introduction | 第56-58页 |
| 2.2 Materials and Methods | 第58-62页 |
| 2.2.1 Reagents and chemicals | 第58页 |
| 2.2.2 Preparation of test substance | 第58页 |
| 2.2.3 Animals and treatment | 第58-59页 |
| 2.2.4 Serum biochemistry | 第59页 |
| 2.2.5 Histopathological examinations | 第59页 |
| 2.2.6 Preparation of hepatic homogenate | 第59-60页 |
| 2.2.7 Determination of hepatic lipid peroxidation,antioxidative defense potential andNO level | 第60页 |
| 2.2.8 Western blot analysis | 第60-61页 |
| 2.2.9 Determination of activation of hepatic caspase-3 | 第61页 |
| 2.2.10 Detection of DNA fragmentation | 第61页 |
| 2.2.11 Statistical analysis | 第61-62页 |
| 2.3 Results | 第62-77页 |
| 2.3.1 BRPS alleviated CCl_4-induced hepatotoxicity dose- and time-dependently | 第62页 |
| 2.3.2 BRPS improved liver histological alterations in CCl_4-challenged mice | 第62页 |
| 2.3.3 BRPS reduced serum ALP activities in CCl_4 exposed mice | 第62-63页 |
| 2.3.4 BRPS reduced serum TNF-α contents in CCl_4 exposed mice | 第63页 |
| 2.3.5 BRPS reduced hepatic TBARS contents in CCl_4 exposed mice | 第63页 |
| 2.3.6 Effect of BRPS on CCl_4-induced alteration of hepatic antioxidant defencepotential | 第63页 |
| 2.3.7 BRPS reduced hepatic NO contents and down-regulated hepatic iNOS andCOX-2 protein expression in CCl_4 exposed mice | 第63-64页 |
| 2.3.8 BRPS suppressed the caspase-3 cleavage and activation in CCl_4 exposedmice | 第64页 |
| 2.3.9 BRPS suppressed hepatic DNA fragmentation in CCl_4 exposed mice | 第64页 |
| 2.3.10 BRPS down-regulated nuclear NF-κB p65 protein expression in livers of CCl_4exposed mice | 第64页 |
| 2.3.11 BRPS suppressed hepatic MAPKs activation in CCl_4 exposed mice | 第64-65页 |
| 2.3.12 BRPS up-regulated hepatic CYP2E1 protein expression in CCl_4 exposedmice | 第65-77页 |
| 2.4 Discussion | 第77-81页 |
| 2.5 Conclusion | 第81-82页 |
| Chapter 3 BRP,a polysaccharide fraction isolated from Boschniakia rossica,protectsagainst galactosamine and lipopolysaccharide induced hepatic failure in mice | 第82-110页 |
| Abstract | 第83-84页 |
| 3.1 Introduction | 第84-86页 |
| 3.2 Materials and Methods | 第86-90页 |
| 3.2.1 Animals | 第86页 |
| 3.2.2 Reagents | 第86页 |
| 3.2.3 Polysaccharides preparation and preliminary chemical analysis | 第86-87页 |
| 3.2.4 Animal treatment | 第87页 |
| 3.2.5 Biochemical analysis of serum | 第87页 |
| 3.2.6 Histopathological examinations | 第87-88页 |
| 3.2.7 Detection of DNA fragmentation | 第88页 |
| 3.2.8 Biochemical determination of liver | 第88页 |
| 3.2.9 Immunoblot anolysis | 第88-89页 |
| 3.2.10 Statistical analysis | 第89-90页 |
| 3.3 Results | 第90-105页 |
| 3.3.1 BRP reduced serum ALT and AST of mice with GalN/LPS induced liverinjury | 第90页 |
| 3.3.2 BRP improved liver histological alterations in GalN/LPS challenged mice | 第90页 |
| 3.3.3 BRP reduced serum TNF-α and IL-6 contents in GalN/LPS challengedmice | 第90-91页 |
| 3.3.4 BRP suppressed hepatic DNA fragmentation and caspase-3 and caspase-8activation in GalN/LPS challenged mice | 第91页 |
| 3.3.5 BRP reduced hepatic LOOH and TBARS contents in GaIN/LPS challengedmice | 第91页 |
| 3.3.6 BRP improved the GalN/LPS induced alteration of hepatic antioxidant defencepotential | 第91页 |
| 3.3.7 BRP up-regulated hepatic HO-1 protein expression in GalN/LPS challengedmice | 第91-92页 |
| 3.3.8 BRP reduced hepatic NO content and down-re:gulated hepatic iNOS and COX-2protein expression in GalN/LPS challenged mice | 第92页 |
| 3.3.9 BRP down-regulated nuclear NF-κB p65 protein expression in livers ofGalN/LPS challenged mice | 第92页 |
| 3.3.10 BRP suppressed hepatic JNK and ERK activation in GaIN/LPS challengedmice | 第92-93页 |
| 3.3.11 BRP down-regulated TLR4 protein expression in livers of GalN/LPSchallenged mice | 第93-105页 |
| 3.4 Discussion | 第105-109页 |
| 3.5 Conclusion | 第109-110页 |
| General Conclusions | 第110-111页 |
| References | 第111-123页 |
| Publications | 第123-125页 |
| 致谢 | 第125页 |
