[Effects of raloxifene combined with conjugated equine estrogen on prothrombotic state in ovariectomized rats]

To study effects of raloxifene (RLX) with different doses of conjugated equine estrogen(CEE) on prothrombotic profiles in the ovariectomized rats model.

Total of 32 healthy female SD rats at age of 9 to 10 months were equally divided into every 8 rats at 4 groups randomly. One week after ovariectomized, they were treated by drugs, including control group with placebo(0.9% Nacl intragastric administration), RLX group with RLX 6 mg/(kg·d), RLX and low CEE group with RLX 6 mg/(kg·d) + CEE 0.07 mg/ (kg·d) and RLX and high CEE group with RLX 6 mg/ (kg·d) + CEE 0.5 mg/ (kg·d) for 10 weeks before death. Thrombin turbidimetry method was used to evaluate the plasma fibrinogen(FIB), transmitting substrate method for antithrombin III(ATIII) activity, double-antibody sandwich ELISA for plasminogen activator inhibitor 1 (PAI-1), D-dimer (D-D) and von Willebrand factor (vWF) and nitrate reductase method for nitric oxide(NO).

(1) Coagulation and anticoagulation indicators: it was observed (1.62 ± 0.22) g/L FIB at control group, (2.02 ± 0.54) g/L at RLX group, (1.97 ± 0.16) g/L at RLX and low CEE group, (2.00 ± 0.18) g/L at RLX and high CEE group. There was a statistically significant difference between control group and any one of treatment groups (P < 0.05) and no statistical significance among those three treatment groups (P > 0.05). No significant change was observed in plasma ATIII activity among groups (P > 0.05). (2) Fibrinolytic and anti-fibrinolytic indicators: it was observed (14.1 ± 2.8) µg/L PAI-1 at control group, (20.0 ± 3.3) µg/L at RLX group, (41.5 ± 5.5) µg/L at RLX and low CEE group, (38.9 ± 6.0) µg/L at RLX and high CEE group. A remarkable increase was observed between control group and any one of treatment groups (P < 0.05) . But there was no significant difference of D-D among groups (P > 0.05) . (3) Endothelial function: it was (43 ± 7) % vWF at control group, (49 ± 5) % at RLX group, (46 ± 6) % at RLX and low CEE group, (36 ± 5) % at RLX and high CEE group. The vWF of RLX and high CEE group was the lowest among all groups (P < 0.05) . There was no difference of NO among groups (P > 0.05).

In the different links of thrombosis, RLX gives different function and may increase the risk. CEE plays a synergism role in the matter of fibrinolysis and anti-fibrinolysis with RLX, further giving rise to thrombosis effect of RLX. And it also has a protective role in the function of vascular endothelium to some extent. But this only works with high dose.