基于平衡TF/TFPI水平研究三七在心房颤动大鼠治疗中维持抗凝/出血稳态的作用及机制

的:从平衡组织因子(TF)、组织因子途径抑制物(TFPI)水平角度,研究三七对心房颤动(AF)大鼠眼眦静脉血液TF、TFPI表达水平、血凝系列、抗凝/出血风险的影响,来探讨三七维持抗凝/出血稳态的可能作用机制,为中药抗凝治疗提供理论依据。 方法:以新鲜配置ACh-CaCl₂混合液为造模药物,采用尾静脉注射ACh-CaCl₂混合液建立房颤大鼠模型。将24只大鼠随机分为假手术组、模型组、三七组和华法林组,每组6只。各组给予相应的干预措施。通过M6240C型多道生理信号采集处理系统描记标准Ⅱ导联心电图全程记录,选取心电图典型AF表现的大鼠纳入模型及给药组,直到实验结束。采用酶联免疫吸附法(ELISA)测定血浆 TF、TFPI水平,即时检测技术(POCT)测定血凝系列。 结果:①治疗第3天,与假手术组比较,其他各组TF、TFPI值均明显升高(P<0.05); 华法林组、三七组与模型组相比TF、TFPI均有统计学差异(P<0.05),而华法林组与三七组相比无统计学差异(P>0.05); ②治疗第7天,与假手术组比较,其他各组TF、TFPI值均明显升高(P<0.05); 华法林组、三七组与模型组相比TF、TFPI均有统计学差异(P<0.05); 华法林组与三七组相比TF水平无统计学差异(P>0.05),而TFPI有统计学差异(P<0.05); ③治疗第3天,与假手术组比较,其他各组INR值、PT均明显降低(P<0.05); 模型组、华法林组和三七组相比INR值、PT无统计学差异(P>0.05); ④治疗第7天,与假手术组比较,其他各组INR值、PT均有统计学差异(P<0.05); 华法林组、三七组与模型组对比INR值均有统计学差异(P<0.05),华法林组与三七组对比INR值、PT有统计学差异(P<0.05); ⑤假手术组、模型组、三七组大鼠在建模及治疗期间均未出现皮下出血情况; 华法林组大鼠在治疗第7天出现1只大鼠皮下瘀点。 结论:三七能通过平衡心房颤动大鼠血浆中的TF、TFPI水平,抑制高凝状态,减少血栓栓塞并发症和防止出血,从而维持抗凝/出血的稳态。

Effect and mechanism of Panax notoginseng on maintaining anticoagulation/bleeding homeostasis in rats with atrial fibrillation based on balanced TF/TFPI levels

Objective:To investigate the effects of Panax notoginseng on Tissue factor(TF)and Tissue factor pathway inhibitors(TFPI)expression levels,hemagglutination series,and the risk of anticoagulation/bleeding in eye canthus veins of rats with atrial fibrillation,from the perspective of balancing TF and TFPI levels,to explore the possible mechanism of panax notoginseng in maintaining anticoagulation/bleeding homeostasis,and to provide theoretical basis for traditional Chinese medicine anticoagulation therapy.Methods:Fresh ACh-CaCl₂ mixture was used as the modeling drug,and the rat model of atrial fibrillation was established by injecting ACh-CaCl₂ mixture into tail vein.Twenty-four rats were randomly divided into sham operation group,model group,panax notoginseng group and Warfarin group,with 6 rats in each group.Each group was given corresponding intervention measures.Through type M6240C multi-channel physiological signal acquisition processing system of eeg,standard Ⅱ lead electrocardiogram(ecg)records all the way,the selection of typical AF ecg manifestation rats into the model and give medicine group,until the end of the experiment.The plasma TF and TFPI levels were determined by ELISA and the hemagglutination series were determined by POCT.Results:①On the third day of treatment,the TF and TFPI values of other groups were significantly higher than those of the sham group(P<0.05).There were statistically significant differences in TF and TFPI between the warfarin group and panax notoginseng group compared with the model group(P<0.05),while there were no statistically significant differences between the warfarin group and panax notoginseng group(P>0.05).②On the 7th day of treatment,the TF and TFPI values of other groups were significantly increased compared with the sham group(P<0.05).There were statistically significant differences in TF and TFPI between the Warfarin group and panax notoginseng group and the model group(P<0.05).Compared with panax notoginseng group,there was no significant difference in TF level between warfarin group and panax notoginseng group(P>0.05),while TFPI was significantly different(P<0.05).③On the third day of treatment,INR values and PT in all groups were significantly lower than those in the sham group(P<0.05).There was no statistical difference in INR value and PT between model group,warfarin group and panax notoginseng group(P>0.05).④On the 7th day of treatment,there were statistically significant differences in INR values and PT between the sham operation group and other groups(P<0.05).There were statistically significant differences in INR values and PT between the Warfarin group,panax notoginseng group and the model group(P<0.05),while there were statistically significant differences in INR values and PT between the Warfarin group and the panax notoginseng group(P<0.05).⑤No subcutaneous bleeding occurred in sham operation group,model group and panax notoginseng group during modeling and treatment.On the 7th day of treatment,1 rat of warfarin group presented subcutaneous petechiae.Conclusion:Panax notoginseng can maintain anticoagulation/bleeding homeostasis by balancing TF and TFPI levels in plasma of atrial fibrillation rats,inhibiting hypercoagulability,reducing thromboembolism complications and preventing bleeding.