| Holthuria leucospilota belongsed to Holothuriidea and Holothuroidea, being poisonous, not edible.Holothuria leucospilota acid mucopolysaccharide(HL-P) was extracted from xero-body of holthuria leucospilotas. It was clinically reported that HL-P had therapeutical effect to patients with cerebral embolism during their recovering. This investigation evaluated the therapeutical effect of HL-P to stroke and discuss its mechanisms.HL-P improved the disbalance of behavior that was induced by Fed 3 in rats with cerebral middle artery occlusion(CMAO), treatment with HL-P 1.25, 2.5, 5.0 mg/kg/d for 3 days. Compared with model control, the impairment of nerve function was decreased by 30.1% (PO.01), 43.8%(P<0.001), respectively, after 2.5, 5.0 mg/kg/d HL-P iv infusion for 3 days. And the cerebral infarction area was decreased by 17.0% (P>0.05), 43.9%(P<0.01), 53.8% (PO.001) respectively by iv infusion the three doses of HL-P. Encephaledema compared with model control was decreased by 70.6% (PO.05), 72.5%(P<0.05) by iv infusion of HL-P 2.5, 5.0 mg/kg/d for 3 days. Its intensity of actions was compared to that of Shuxuening Injection at the same dose.After 0.1 -, 0.3> 1.0 mg/kg HL-P iv infusion, Rats venous thrombosis induced by static of blood stream could be inhibited obviously. Compared with model control, the wet weigh of thrombus was decreased by 25.5%(P<0.05), 72.5%(P<0.001), 85.3% (PO.001). And the dry weigh of thrombus compared with model control was decreased by 18.5%(P>0.05), 67.7%(P<0.001), 84.6%(P<0.001). Its intensity of actions was compared to that of Shuxuening Injection at the same dose.The anticoagulative activity of HL-P in rats was observed in vivo. After 0.1, 0.3 or 1.0 mg/kg HL-P iv infusion, compared with model control, APTT was prolonged by 0.5%(P>0.05), 28.2%(P<0.001), 145.8% (PO.001), respectively, TT was prolonged by 6.9%(P>0.05), 13.7%(P>0.05), 26.0%(P<0.05), and PT was not changed significantly. The anticoagulative action of HL-P (1.0 mg/kg) could be corrected completely by protamine sulfate(3 mg/kg). But Shuxuening Injection had no the activity.The anticoagulative action of HL-P in rabbits was observed in vitro. It was demonstrated that the anticoagulative effect of HL-P was prominent. The potency action was positively correlated to drug concentration. Minimal HL-P concentrations which prolonged TT, APTT, PT significantly were 1.0, 0.8, 8.2yg/ml, respectively. The anticoagulative action could be corrected by protamine sulfate. It indicated that HL-P was a kind of safe medicine. Shuxuening Injection has not anticoagulative activity.HL-P could not affect content of FIB in normal plasma. The anticoagulative mechanism of HL-P was not as identical as heparin. It was demonstrated that the anticoagulativity of HL-P was not depended on AT-III, and was not Inhibited by PF4. HL-P maybe directly affect thrombin activity.It could conclude that HL-P was a favorable drugs for stroke therapy, which be able to decrease the size of cerebral infarction and encephaledema. The antithrombotic effect of HL-P was related to Its anticoagulative action. And the anticoagulative action of HL-P depended on neither AT-III nor PF4. It may be related to the function of restraining thrombin directly. |
