목차

I. INTRODUNTION 1
A. The role of platelets in cardiovascular diseases 1
B. Antiplatelet therapy in cardiovascular diseases 1
C. Rhubarb and its components 2
D. The signaling molecules in collagen-induced platelet aggregation 3
E. Aims of study 5
II. MATERIALS AND METHODS 6
1. Materials 6
2. Plant material 7
3. Extraction and isolation 7
4. Animals 8
5. Preparation of platelets 9
6. In vitro platelet aggregation study 10
7. Platelet secretion study (ATP release) 10
8. Determination of cytotoxicity 11
9. Ex vivo platelet aggregation study and anticoagulation assay 11
10. Measurement of thromboxane A2 (TXA2) formation 12
11. In vivo mice tail bleeding times 13
12. Measurement of platelet phosphatidylserine (PS) exposure 13
13. Western blot analysis 14
14. Immunoprecipitation and kinase assay 15
15. Statistical analysis 16
III. RESULTS 17
A. Dose-dependent inhibitory effect of rhubarb extract on platelet aggregation in vitro 17
B. Inhibitory effect of four anthraquinone derivatives on platelet aggregation in vitro 19
C. Inhibitory effect of chrysophanol-8-O-glucoside on in vitro and ex vivo platelet aggregation and in vivo mice bleeding time 22
D. Effect of chrysophanol-8-O-glucoside on coagulation 28
E. The activation of platelet intracellular signaling in collagen-induced platelet aggregation 32
F. Effect of inhibitors on collagen-induced activation of PLCγ2/MAPKs/Akt and platelet functional responses 34
G. The activation of PKC isoforms in collagen-induced platelet aggregation 39
H. Effect of PKCε inhibitor on collagen-induced activation of PLCγ2/MAPKs/Akt and platelet functional responses 41
I. Effect of chrysophanol-8-O-glc on platelet signaling pathway and functional responses 45
IV. DISCUSSION 50
V. CONCLUSION 55
REFERENCES 56
국문요약 68