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目的比较水蛭提取物结肠迟释微丸(colon delayed-release pellets,CDP)和水蛭提取物普通微丸(regular pellets,RP)的抗凝血和抗血栓形成作用。方法采用毛细管法检测新西兰兔凝血时间,考察CDP和RP对大鼠动-静脉旁路血栓、狭窄法诱导的下腔静脉血栓和三氯化铁(FeCl_3)诱导颈动脉血栓形成的作用。凝血时间测定实验为单次给药,设3个组:正常组,CDP组(64 mg·kg~(-1)·d~(-1))和RP组(43.7 mg·kg~(-1)·d~(-1));动-静脉旁路血栓实验为单次给药,设6个组:模型组,CDP低、高剂量组(87,174 mg·kg~(-1)·d~(-1)),RP低、高剂量组(59.4,118.8mg·kg~(-1)·d~(-1)),阿司匹林组(7.8 mg·kg~(-1)·d~(-1));狭窄法诱导大鼠下腔静脉血栓实验设8组:假手术组,模型组,CDP低、高剂量组,RP低、高剂量组,阳性药华法林组(2.0 mg·kg~(-1)·d~(-1))和活血通脉胶囊组(312.5 mg·kg~(-1)·d~(-1)),每天给药1次,连续给药7 d;FeCl_3诱导颈动脉血栓实验为单次给药,设8组:假手术组,模型组,CDP低、高剂量组,RP低、高剂量组,阳性药氯吡格雷组(30 mg·kg~(-1)·d~(-1))和活血通脉胶囊组。称量动-静脉旁路血栓湿重和干重以及静脉血栓质量和长度,计算血栓形成抑制率;对动脉血栓进行半定量病理学分析,计算血栓形成百分比和血栓形成抑制率。结果与正常组比较,CDP组和RP组分别在给药后4 h和0.5 h显著延长新西兰兔凝血时间(P<0.05),抗凝作用分别维持4 h和1 h。CDP组和RP组能剂量依赖性抑制大鼠动-静脉旁路血栓和下腔静脉血栓形成,抑制动脉血栓形成,与模型组比较,差异有统计学意义(P<0.01)。此外,在抑制大鼠动-静脉旁路血栓和下腔静脉血栓作用上,CDP强于RP。结论 CDP抗血栓形成作用显著优于RP,且CDP抗静脉血栓的作用比抗动脉血栓明显。
Objective To compare anticoagulant and antithrombotic effects of leech extract colonic delayed-release pellets (CDP) and leech extract regular pellets (RP). Methods The clotting time of New Zealand rabbits was detected by capillary method. The effects of CDP and RP on carotid artery thrombosis induced by arterio - venous bypass thrombosis and stenosis were investigated. The clotting time was measured in a single dose. The three groups were as follows: normal group, CDP group (64 mg · kg -1 · d -1) and RP group (43.7 mg · kg -1 ) · D ~ (-1)). The arterial - venous bypass thrombosis experiment was a single administration, and there were 6 groups: model group, low and high CDP group (87,174 mg · kg -1 · d ~ (-1), RP low and high dose groups (59.4 and 118.8 mg · kg -1 · d -1), aspirin group (7.8 mg · kg -1 · d -1) 1)); Stenosis-induced rat IVC thrombosis was divided into 8 groups: sham operation group, model group, CDP low and high dose group, RP low and high dose group, the positive drug warfarin group (2.0 mg · kg (-1) · d -1 and 312.5 mg · kg -1 (-1) · d -1, respectively, once a day for 7 days. The experiment of FeCl_3-induced carotid artery thrombosis was a single administration. Eight groups were divided into sham operation group, model group, CDP low and high dose group, RP low and high dose group, positive clopidogrel group (30 mg · kg ~ -1) · d ~ (-1)) and Huoxuetongmai Capsule group. The wet weight and dry weight of arterial-venous bypass thrombus and the quality and length of venous thrombus were weighed, and the inhibition rate of thrombosis was calculated. The arterial thrombus was semi-quantitatively analyzed for histopathology, and the percentage of thrombosis and thrombosis inhibition rate were calculated. Results Compared with the normal group, the clotting time of New Zealand rabbits was significantly prolonged at 4 h and 0.5 h (P <0.05). The anticoagulant effects were maintained for 4 h and 1 h respectively. CDP group and RP group inhibited the arterio-venous bypass thrombosis and vena cava thrombosis and inhibited arterial thrombosis in a dose-dependent manner in rats. Compared with the model group, the difference was statistically significant (P <0.01). In addition, CDP is stronger than RP in inhibiting the arterio-venous bypass thrombosis and IVC thrombosis in rats. Conclusion The antithrombotic effect of CDP is significantly better than that of RP, and the anti-venous thrombosis of CDP is more effective than anti-thrombosis.