心脏手术患者肝素敏感性与AT-Ⅲ和FX之间的相关性研究

Correlation between heparin sensitivity and AT-Ⅲand FX in patients undergone cardiac surgery

目的探讨心脏手术患者不同个体肝素敏感性的差异与抗凝血酶Ⅲ(AT-Ⅲ)和凝血因子X(FX)的mRNA及蛋白水平之间的相关性,为临床实现个体化的肝素抗凝提供理论依据。方法根据心脏手术患者首次给予肝素剂量(2.5 mg/kg)后的抗凝血效应(ACT)的不同,将患者分为3组:A组:低敏感组(ACT<480 s),B组:敏感组(480 s<ACT<750s);C组:超敏感组(ACT>750 s)。分别在术前留取血标本,应用RT-PCR技术检测AT-Ⅲ和FX基因mRNA的表达,ELISA检测AT-Ⅲ和FX的血浆蛋白质水平。结果本研究共纳入实施心脏手术的成年患者195例,3组AT-ⅢmRNA表达量随肝素敏感性增高而增高,两者呈正相关,3组FXmRNA表达量与肝素敏感性呈负相关。C组与A组AT-ⅢmRNA和FXmRNA的表达量差异均具有统计学意义(P<0.05)。AT-Ⅲ和FX蛋白定量分析表明,3组FX蛋白水平间mRNA表达趋势一致并呈负相关,C组分别与A组和B组相比,FX的蛋白水平差异均具有统计学意义(P<0.05);而B组AT-Ⅲ蛋白水平显著低于A组和C组(P均<0.05);结论心脏手术患者不同个体间肝素敏感性的差异与AT-Ⅲ和FX基因的mRNA表达量及血浆蛋白水平差异有关。

Objective To investigate the correlation between heparin sensitivity and mRNA and protein levels of AT-Ⅲand FX in patients undergone cardiac surgery and to provide a theoretical basis for individualized heparin anticoagulation in clinical practice.Methods Patients undergonecardiac surgery were divided into three groups according to ACT after initial heparin dosing(2.5 mg/kg):insensitive group(group A,ACT<480 s),sensitive group(group B,480 s<ACT<750 s),and hypersensitive group(group C,ACT>750 s).Blood samples were obtained before thesurgery to determine the mRNA levels of antithrombinⅢ(AT-Ⅲ)and factor X(FX)using reverse transcription-polymerase chain reaction(RT-PCR)assays and the plasma protein levels of AT-Ⅲand FX using enzyme-linked immunosorbent assays(ELISAs).Results The mRNA level of AT-Ⅲsuccessively increased from group A to group C and was positively correlated with the heparin sensitivity;the mRNA level of FX was negatively correlated with the heparin sensitivity;a significant difference was observed between groups A and C(P<0.05).The protein level of FX showed the same trend as its mRNA level and was negatively correlated with the heparin sensitivity,with a significant difference between groups A and B,and between groups B and C(P<0.05).The protein level of AT-Ⅲwas significantly lower in group B than in groups A and C(P<0.05).Conclusion Individual variation in the heparin sensitivity is significantly correlated withthe mRNA and plasma protein levels of AT-Ⅲand FX.