Modulation of Permeability--Glycoprotein by Quercetin and Its Effect on Efflux Transport of Ivermectin in Rats

目录

声明

论文说明

CONTENTS

摘要

ABSTRACT

ABBREVIATIONS

CHAPTER 1 General introduction and review of the literature

1．1 Background of P-gp

1．2 Structure and mechanism of P-gp mediated efflux

1．3 Modulation of P-gp

1．3．1 Modulation of P-gp by cytokines

1．3．2 Modulation of P-gp via nuclear orphan receptors

1．3．3 Modulation of P-gp through Nitric oxide(NO)

1．3．5 Modulation of P-gp by miscellaneous factors

1．4 Role of quercetin in the modulation of P-gp

1．5 Summary and objectives

REFERENCES

CHAPTER 2 Modulation of P-gp by quercetin in Caco-2 cells

2．1 Introduction

2．2．Materiais and methods

2．2．1 Reagents and drugs

2．2．2 Cells，cell culture，and conditions

2．2．3 The Caco-2 cells viability assay(MTT)

2．2．6 The P-gp expression by immunoblot in Caco-2 cells

2．2．7 The P-gp expression by immunofluorescence staining in Caco-2 cells

2．2．8 Data analysis

2．3 Results

2．3．2 Effect of quercetin on P-gp ATPase and ATP activity

2．3．3 Effect of quercetin on Mdr1，PXR and CAR mRNA level

2．3．4 Effect of quereetin on P-gp expression

2．3．5 Effect of quercetin on P-gp protein expression by immunofluorescence in Caco-2 cells

2．4 Discussion

REFERENCES

CHAPTER 3 Effect of quercetin on P-gp localization in tissues of rat

3．1 Introduction

3．2 Materials and methods

3．2．1 Chemicals and drugs

3．2．2 Animals and management

3．2．3 Treatment and sampling

3．2．5 Data analysis

3．3 Results

3．3．2 Effect of quercetin on P-gp localization in kidney and ileum of rats

3．4 Discussion

REFERENCES

CHAPTER 4 Effect of quercetin on P-gp expression in the tissues of rats

4．1 Introduction

4．2 Materials and methods

4．2．1 Chemicals and reagents

4．2．2 Animals and management

4．2．3 Treatment and sampling

4．2．4 The mRNA expression of Mdrla，Mdrlb，PXR and CAR

4．2．5 The P-gp protein expression by immunoblot in liver and jejunum

4．2．6 Molecular modeling of quercetin with PXRand CAR

4．2．7 Statistical analysis

4．3 Results

4．3．2 Effect of quercetin on Mdr1b mRNA expression

4．3．3 Effect of quercetin on PXR mRNA expression

4．3．4 Effect of quercetin on CAR mRNA expression

4．3．5 Modulation of P-gp expression by quercetin

4．3．6 Molecular modeling of quercetin with PXR and CAR

4．4 Discussion

REFERENCES

CHAPTER 5 Effect of quercetin on transmembrane transport of ivermectin by in Situ perfusion

5．1 Introduction

5．2 Materials and methods

5．2．1 Chemicals and reagents

5．2．2 Animals and management

5．2．3 Treatment and sampling

5．2．4 In situ perfusion in rat

5．2．5 HPLC assay for ivermectin

5．2．6 Statistical analysis

5．3 Results

5．3．1 Chromatographic detection and a standard curve of ivermectin

5．3．2 Evaluation of P-gp function by ivermectin uptake after quercetin administration in the rat

5．4 Discussion

REFERENCES

GENERAL CONCLUSION

INNOVATION

PUBLICATIONS

ACKNOWLEDGMENTS