| This dissertation is composed of three chapters. The first chapter discussed Rubus spp.Blackberry about plasma coagulation parameters, fibrinolytic activity and fibrinolytic inhibition activity in vitro. The antithrombotic effect of extract from Rubus spp.Blackberry in vivo. The second chapter studied the antithrombotic effect of extract and active compounds from the Paeonia lactiflora Pall in vivo. The third chapter summarized the thrombus formation and researched progress of antithrombotic drugs.Chapter 1. The thrombus formation and researched progress of antithrombotic drugsSummary of the three factors of thrombosis: First, endothelial dysfunction. Second, platelet aggregation and activation of blood coagulation. Third, the change of hemodynamic character, such as blood flow slows down, the formation of eddies and so on. Researching progress of antithrombotic drugs included anticoagulant drugs, platelet aggregation inhibitor drugs and thrombolytic drugs.Chapter 2. The antithrombotic effect of Rubus spp.BlackberryThis chapter includes four parts. Part 1: The Rubus spp.Blackberry extract was evaluated by activated partial thromboplastin time(APTT), thrombin time(TT), prothrombin time(PT), and fibrinogen(FIB) assays for the first time in vitro. Results indicated that total ethanol, Petroleum ether, n-butyl alcohol extract of Rubus spp.Blackberry and eight compounds(hexadecanoic acid, 1α, 2α, 3β, 19α-tetrahydroxyurs-12-en-28-oicacid, tormentic acid, ursolic acid, 9(Z)-octadecenamide, suavissimosid R1, pomolic acid-28-O-β-D-glucopyranosylester, 3,5,7,2’,5’-pentahydroxyflavan)exhibited the anticoagulant activity. Petroleum ether extract of Rubus spp.Blackberry, euscaphic acid and oleanolic acid exhibited the procoagulant activity.Part 2: By establishing the fibrinolytic pathway inhibitory model in vitro. Results indicated that only total ethanol and n-butyl alcohol extract of Rubus spp.Blackberry had some fibrinolytic activity. Total ethanol, Petroleum ether, n-butyl alcohol extract of Rubus spp.Blackberry and ten compounds had the fibrinolytic inhibitory activity.Part 3: Subcutaneous injection of norepinephrine combined with ice water bath was used to establish the acute blood stasis rat model and the antithrombotic effects and mechanism were investigated by the acute blood stasis rat model for the first time. Results indicated that the extract of Rubus spp.Blackberry had antithrombotic activity. Then in administration groups, WBV, PV, PCV and ESR significantly decreased, suggesting that the amelioration effect of Rubus spp.Blackberry on PV might be partly due to the ESR decrease, the amelioration effect of Rubus spp.Blackberry on WBV might be partly due to the PCV decrease. The beneficial effect of Rubus spp.Blackberry extract on intrinsic and extrinsic coagulation pathways, and hinder fibrin formation. Our study results suggested that Ret, Rpe, Rea and Rbu groups might significantly down regulate serum TXB2 level and up regulate serum 6-keto-PGF1α level in blood stasis rat, indicating that the antithrombotic action of effect of Rubus spp.Blackberry was associated with the regulation of TXA2 and PGI2. Results indicated that the effect of Rubus spp.Blackberry has a protective effect on vascular endothelium, and can regulate the tension of vascular smooth muscle by down-regulating ET-1 level and up-regulating eNOS level.Part 4: The ursolic acid antithrombotic effects and mechanism were investigated by the acute blood stasis rat model for the first time. Results indicated that the ursolic acid had antithrombotic activity. The ursolic acid reduced WBV might be partly due to the PCV decrease, reduced PV might be partly due to the ESR decrease. The beneficial effect of ursolic acid on intrinsic and extrinsic coagulation pathways, and hinder fibrin formation. Our study results suggested that ursolic acid groups might significantly down regulate serum TXB2 level and up regulate serum 6-keto-PGF1α level in blood stasis rat, indicating that the antithrombotic action of ursolic acid was associated with the regulation of TXA2 and PGI2. Results indicated that the effect of ursolic acid has a protective effect on vascular endothelium, and can regulate the tension of vascular smooth muscle by down-regulating ET-1 level.Chapter 3. The antithrombotic effect of Paeonia lactiflora PallPart 1: The antithrombotic effects and mechanism of Paeonia lactiflora Pall were investigated by the acute blood stasis rat model for the first time. Results indicated that the extract of Paeonia lactiflora Pall had antithrombotic activity. The extract of Paeonia lactiflora Pall reduced WBV might be partly due tothe PCV decrease, reduced PV might be partly due to the ESR decrease. The beneficial effect of it on intrinsic and extrinsic coagulation pathways, and hinder fibrin formation. Total ethanol extract and ethyl acetate extract of Paeonia lactiflora Pall could regulate the tension of vascular smooth muscle by down-regulating ET-1 level and up-regulating eNOS level. The n-butyl alcohol extract of Paeonia lactiflora Pall could up-regulating eNOS level. The Pet, Pea and Pbu groups might significantly down regulate serum TXB2 level and up regulate serum 6-keto-PGF1α level in blood stasis rat, indicating that the antithrombotic action of effect of Paeonia lactiflora Pall were associated with the regulation of TXA2 and PGI2.Part 2: The antithrombotic effects and mechanism of four compounds(protocatechuic acid, albiflorin, paeoniflorin, 1,2,3,4,6-O-pentagalloyglucose) from Paeonia lactiflora Pall were investigated by the acute blood stasis rat model for the first time. Results indicated that they had antithrombotic activity. And they reduced WBV might be partly due to the PCV decrease, reduced PV might be partly due to the ESR decrease. The beneficial effect of they on intrinsic and extrinsic coagulation pathways, and hinder fibrin formation.Paeoniflorin and albiflorin could regulate the tension of vascular smooth muscle by down-regulating ET-1 level and up-regulating eNOS level. Protocatechuic acid and 1,2,3,4,6-O-pentagallox-yglucose could up-regulating eNOS level. Albiflorin and 1,2,3,4,6-O-pentagalloyglucose could down regulate serum TXB2 level and up regulate serum 6-keto-PGF1α level in blood stasis rat, protocatechuic acid could up regulate serum 6-keto-PGF1α level in blood stasis rat, indicating that the antithrombotic action were associated with the regulation of TXA2 and PGI2. |
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