Experimental Study Of The Role Of Blood Circulation And The Mechanism Of The Antithrombotic Effect Of Safflower Extract

Safflower injection is safflower sterilization water solution, which had been extracted, with the efficacy of activating blood and absorb clots, mainly used to the treatment of cerebral vascular infarction, coronary heart disease and vasculitis in clinical. To reduce toxicity and the incidence of adverse reactions, improve the content of active substances, the enterprises take modern technical methods of Chinese medicine to improve its process. The main purpose of this paper is to evaluate reasonable of the process and clarify the antithrombotic mechanism of safflower extract, by systematically study on the pharmacodynamics of safflower extract.The canine model of anesthetized open chest and coronary artery occlusion causing by coronary artery ligation, had been used to study the anti-myocardial ischemia effects of safflower extract on anesthetized canine, by recording the creatine kinase (CK) and lactate dehydrogenase (LDH). The results show that in the selected dose range, the downtrend of heart rate, mean arterial pressure, left ventricular pressure, cardiac output, increased rate of ventricular contraction, stroke excretion, cardiac index, left ventricular work, myocardial oxygen consumption of canine acute myocardial ischemia model can be alleviated. There were significant differences in mean arterial pressure, left ventricular pressure, cardiac output, cardiac index, left ventricular work, the change rate of myocardial oxygen consumption among the 1.0g, 0.5g crude drug/kg of safflower extract and 0.5g crude drug/kg of commercial safflower injection groups at 60',90',120',180'some time points after administration (P<0.05 or P<0.01). This part of study aslo show that creatine kinase (CK), lactate dehydrogenase (LDH) and myocardial infarct size of 1.0g,0.5g,0.25g crude drug/kg of safflower extract and 0.5g crude drug/kg of commercial safflower injection groups were significantly lower than the corresponding values of control group after administration at 120'or 180'time points (P<0.05) The quantitative test of myocardial infarction showed that:myocardial infarct size of 1.0g,0.5g, 0.25g crude drug/kg) of safflower extract groups was significantly lower than the control group (P<0.05 or P<0.01).The myocardial ischemia rats causing by injecting pituitrin had been used to study the protection effects on animals with myocardial ischemia of safflower extract, safflower extract of improved process and commercial safflower injection had a significant confrontation on myocardial ischemia induced by pituitrin, and reducd the deviation degree of LeadⅡand precordial ST segment (P< 0.05 or P<0.01); 3.33g,1.67g/kg safflower extract and 1.67g/kg of commercial safflower injection groups can reduce the incidence of myocardial ischemia of rats (P<0.05 or P<0.01).The acute experimental model of incomplete cerebral ischemia causing by bilateral carotid artery ligation, had been used to study the influence of safflower extract on the animal brain index by recording the brain water content, capillary permeability, and brain tissue pathological changes. The results show that brain water content and cerebral index of the cerebral ischemia model had significantly increased compared with the corresponding value of pseudo operation group, while brain water content of 3.33g/kg of safflower extract and 1.67g/kg of commercial safflower injection groups was significantly reduced (P<0.05 or P<0.01). The content of Evans Silan within the brain tissue of 3.33g,1.67g,0.84g/kg of safflower extract groups significantly reduced (P<0.05 or P<0.01), means that the drug can reduce the cerebral vascular permeability; by observing the cerebral morphology show that the number or degree of affected nerve cells of each administration group was significantly less than the operation model group; nuclei by deeply stained or nucleoli disappearanced lightly, which suggested that the drug had a protective effect on the acute cerebral ischemia of animals.For the cerebral circulation impairment mice with ligation both sides of the carotid artery and vagus nerve,3.33g,1.67g/kg of safflower extract and 1.67g/kg of commercial safflower injection groups can significantly longer the survival time of mice (P<0.01).Using rat neck artery-vein bypass in vitro thrombosis mode, the thrombus weight of the high, medium dose group and commercial safflower injection group could be significantly reduced (P<0.05 or P<0.01).The acute blood stasis model rats causing by subcutaneous injecting epinephrin hydrochloride had been used to study the hemorheology effect of safflower extract. The results show that the whole blood contrast viscosity and hematocrit of 3.33g,1.67g,0.84g/kg of safflower extract and 1.67g/kg of commercial safflower injection groups could be significantly reduced in acute blood stasis model rats. The maximum platelet aggregation rate of 3.33g,1.67g/ kg of safflower extract and 1.67g/kg of commercial safflower injection groups could be reduced in normal rats (P<0.05 or P<0.01).The endothelial cell injury rat model causing by injecting epinephrin hydrochloride had been used to clarify the antithrombotic mechanism of safflower extract, by recording the thromboxane B2 content, prostaglandin hormone levels and activity of plasminogen activator inhibitor. The results show that the 3.33g,1.67g/kg of safflower extract groups could increase the 6-Keto-PGFla/TXB2 ratio of the endothelial cell injury rat, while 3.33g/kg safflower extract group significantly reduce plasma PAI activity of the endothelial cell injury rat (P<0.05). Show that the antithrombotic mechanism of safflower extract has a relationship with inhibiting the synthesis of thromboxane A2, and promoting the synthesis of prostacyclin, decreasing the activity of plasma plasminogen activator inhibitor.In summary, safflower extract of improved process had the effect on anti-myocardial ischemia, antithrombotic, anti-cerebral ischemia, anti-platelet aggregation, improve hemorheology, anti-cerebral circulation disorder, and the antithrombotic mechanism had a relationship with inhibiting the synthesis of thromboxane A2, and promoting the synthesis of prostacyclin, decreasing the activity of plasma plasminogen activator inhibitor. The pharmacological study verified the effectiveness of process improvement.