Preliminary Study On The Effect And Mechanism Of Kangxueshuanyihao

Objective:This study was designed to observe the effects of Kangxueshuanyihao on experimental thrombosis animal models as well as hemorheology, microcirculation and platelet aggregation; and to study and preliminarily explore its mechanism of action to provide scientific basis for further development of this drug.Methods:(1) The effects of Kangxueshuanyihao on cerebral thrombosis sepuel of rats induced by FeCl3. Rats were intragastrically given 2g,4g,8g/kg of Kangxueshuanyihao, positive control of 50mg/kg brevisapin tablets or 50mg/kg nimodipine tablets. Drugs were preliminarily administered once daily for 7 days to all rats. Focal cerebral infarctions of rats were induced by middle cerebral artery occlusions (MC AO) 1 h after the last dosage. The effect of Kangxueshuanyihao on the behaviors, infarct areas and pathomorphology of brain tissue in MCAO rats were evaluated. (2)The antithrombotic effect of Kangxueshuanyihao was investigated through in vivo test of thrombosis induced by electrical stimulation in rats.3 groups of rats were randomly administered with 1 g,2g and 4g/kg Kangxueshuanyihao crude drug, respectively and positive control group received 1 OOmg/kg aspirin. Each group was intragastrically administered once daily for 10 days. Thromboses were induced by electrical stimulation 1 h after the last dosage and thrombosis length was measured as the main outcome index. (3) The effect of Kangxueshuanyihao on the thrombosis in mice induced by collagen and epinephrine. Mice were randomly assigned to administration of Kangxueshuanyihao 2g,4g and 8g crude drug/kg, respectively. Positive control group was given 30mg/kg of Brevisapin Tablets. Each group was intragastrically administered once daily for 5 consecutive days. Thromboses of mice were induced using collagen 1h after the last dosage. The number of hemiplegia recovery in 15 min was recorded as the main obvervational index.3 groups of rats were administered with 1g,2g and 4g/kg Kangxueshuanyihao, respectively and positive control group received 100mg/kg of aspirin. Each group was intragastrically administered once daily for 10 consecutive days. Thromboses were induced by electrical stimulation 1 h after the last dosage and thrombosis length was measured as the main outcome index. (4) The effect of Kangxueshuanyihao on the inhibition of platelet aggregation induced by ADP. Rats were assigned to Kangxueshuanyihao 2g,4g and 8g /kg dosage groups.50mg/kg brevisapin tablets was used as positive control. Rats were intragastrically administered once daily for 5 days, and the inhibition of platelet aggregation was compared among the groups. The difference between the inhibitions of groups of Kangxueshuanyihao and positive control were compared, and the statictis of the results was carried out by T-test. (5) Effects of Kangxueshuanyihao on the mice auricle microcirculation disturbance induced by epinephrine. Mice were given 1 g,2g and 4g/kg of Kangxueshuanyihao, once daily for 5 days, respectively. Single dose of 20mg/kg Raceanisodamine Hydrochloride was intraperitoneally administered on experiment day. The effects of the Kangshuanyihao on hemorheology were observed.Results:(1) Behavioral disorders of MCAO rats were significantly improved in 2g and higher dosage groups of Kangxueshuanyihao. Less cellular degeneratiaon and necrosis and infarction area was observed in the highest dosage group, suggesting that the tested drug has could obviously improve the behavioral disorders and organic brain diseases caused by focal cerebral infarction. However, no significant effect on cerebral index brain water content was observed. (2) Numbers of hemiplegia recovery was increased in mice received 8g/kg of Kangxueshuanyihao crude drug, suggesting that the tested drug had a distinct inhibition on the experimental thrombosis of rats in vivo. (3) 1g/kg and higher dosage of the crude drug prolonged the OT value and thrombus length of the rats was markedly shortened in a dose-dependent manner, indicating that the tested drug had a distinct inhibition on the experimental thrombosis of mice in vivo induced by collagen and epinephrine. (4) The inhibition of platelet aggregation in the highest dosage group of Kangxueshuanyihao was significantly higher than brevisapin tablets group, illustrating great superiority of kangshuanyihao in the anticoagulant aspect. (5) Remarkable increase in calibers of mice arteriole and veinule were observed in the mice with 2g/kg and higher dosage of Kangxueshuanyihao and speed of blood flow in veinule were raised in 4g crude drug/kg group, demonstrating noticeable improvement of mice auricle microcirculation by the drug.Conclusion:Kangxueshuanyihao can markedly ameliorate cerebral thrombosis sepuel of rats induced by FeCl3 and exhibit antithrombotic effect on thrombosis model induced by electric stimulation and various platelet aggregation inducers. The antithrombotic mechanism maybe associated with inhibition of platelet aggregation induced by collagen, epinephrine and ADP. Kangshuanyihao can also expand the venule and arteriole and speed up blood flow velocity in venule and promoting venous blood flow velocity. This effect maybe due to its major component breviscapine. The above two types of effects may form the pharmacological basis of Kangshuanyihao ameliorating cerebral thrombosis sepuel of rats.