Comparison between phytoestrogen α-zearalanol and supplementary ectogenesis 17 β-estradiol in the effect on coagulation and fibrinolysis in ovariectomized rats

Wen WANG; Guangjin ZHU

ABSTRACT

BACKGROUND:

α-zearalanol, a natural phytoestrogen has the effect of anti- atherosclerosis like the estrogen but with less side effect. Therefore, it has a potential for more application in the future.

OBJECTIVE:

To investigate the effect of 17β-estradiol (E2) and α-zearalanol (ZAL) on coagulation and fibrinolysis in ovariectomized rats and to compare and analyze their effects.

DESIGN:

An observational and controlled experiment.

SETTING:

Department of Pathophysiology of the Capital University of Medical Sciences and the Department of Pathophsiology of the Institute of Basic Medical Sciences of Chinese Academy of Medical Sciences and Peking Union Medical College. MATERIALS The experiment was completed at the Science Department of Experiment Animals from July to September 2003. Thirty-six healthy female Wistar rats aged 12-week old , weighing (250±10)g, clean grade were involved. The animals were divided into 4 groups, namely sham-operation control group, ovariectomy (OVX) group, OVX +E2 group, OVX+ZAL group with 9 rats in each group.

METHODS:

For the rats in the sham-operation control group, operation was performed without removing the ovary. For the rats in the OVX group,ovariectomy was performed and the rat models were made at the sterile condition. 1 mg/kg 17β-estradiol and 1mg/kg α-zearalanol were respectively injected intramuscularly into the rats in the OVX +E2 group and OVX+ZAL group 14 days after the operation, once every three days for 35days altogether. After the administration of 17β-estradiol or α-zearalanol for 5 weeks, rats were killed, and blood was collected through the common carotid artery and plasma was collected from it. The prothrombin time (PT)and the activated partial thromboplastin time (APTT) were determined with coagulation method. The level of fibrinogen (FG) was measured with an automatic biochemistry analyzer. Tissue factor(TF)level was determined with ELISA method, the activity of tissue plasminogen activator(t-PA)and plasminogen activator inhibitor type 1 (PAI-1)were determined with chromogenic substrate assay. At the same time, the uteri were cut off and weighed by an electronic scale to work out the uteri weight/body weight (g/kg). MAIN OUTCOME

MEASURES:

① PT, APTT, FG,TF, t-PA, PAI-1; ②uteri mass/body mass

RESULTS:

All the 36 rats entered the stage of the result analysis. ①change of PT it was shorter in the OVX group than that in the sham-operation control group (P ＜ 0.01 ), but it was longer than that in the OVX group after supplementation of E2 and ZAL (P ＜ 0.05-0.01 ). ② Change of FG and TF they were significantly higher than those in the sham-operation control group (P ＜ 0.05-0.01 ). But, they were lower than those in the OVX group after supplementation of E2 and ZAL (P＜ 0.05-0.01 ). ③Change of tPA It was significantly lower in the OVX group than that in the sham-operation control group [(0.33±0.33) μkat/L,(4.00±1.50) μkat/L,(q=9.43, P ＜ 0.01 )]. However, it was significantly higher than that in the OVX group after supplementation of E2 and ZAL [(1.83 ±0.67)μkat/L,(1.17±0.83) μkat/L, (q=13.50, P ＜ 0.01; q=5.00, P ＜ 0.05). ④ Change of PAI-1 It was significantly higher than that in the sham-operation control group [(2.33±0.67) μkat/L,(1.17±0.33) μkat/L,(q=10.5, P ＜ 0.01 )]. ⑤Uteri mass/body mass It was significantly lower in the OYX +ZAL group than that in the OVX+ E2 group [0.66,1.96, (q=14.67, P ＜ 0.01)].

CONCLUSION:

Both 17β-estradiol and α-zearalanol can resume the balance of coagulation-fibrinolysis of ovariectomized rats, suggesting that αzearalanol has a similar protective effect similar to that of 17β-estradiol on cardiovascular system. As α-zearalanol has less adverse effect on uteri enlarging than 17β-estradiol, it has a better prospect for substitution of estrogens as a natural phytoestrogen.