静脉导管留置致导管相关性血栓形成药物干预机制的研究

Intravenous indwelling catheter has become a common device in intravenous infusion therapy, whereas catheter related thrombosis is the most common complication of lien, which often leads to health risk, the increased cost of time and treatment expenses for the patient in the hospital. The reasons for the occurrence of catheter related thrombosis are mostly related to endothelial cell injury, blood flow state changes and blood high condensation state. Based on the former study of our research course, we found that anisodamine has good curative effects on the prevention and cure of chemotherapy phlebitis, but the exact mechanism has not been clarified. We adopt enzyme-linked immunosorbent assay (ELISA) method, immune transmission turbidity method to detect rabbit Intravenous indwelling catheter venipuncture model and clinical tube usage patients use low molecular weight heparin (LMWH), anisodamin, form intervention serum thrombosis related markers of von Willebrand Factor (vWF), D-Dimer etc, highly sensitive C-reactive protein (hs-CRP)to reflect and the change of the index of blood rheology, from the perspectives of the vascular endothelial injury, blood coagulation state, inflammation factors influence to analyze the effects after drug intervention. It strives to clarify the mechanism of action for anisodamine, which changes through blood rheology and reduce inflammation factors of the blood vessel damage and low molecular weight heparin play anticoagulant effect, which can reduce the catheter related thrombosis, for catheter related thrombosis and provided the new targets. This research topic has great significance in guiding the safe usage of retained Intravenous indwelling catheter.

静脉留置导管已是静脉输液的常用器械，而导管相关性血栓形成是常见并发症，导致医疗纠纷和医护风险增高、患者住院时间和治疗成本增加。导管留置造成血管损伤被认为是血栓形成的始动因素，而且还与血流状态、血液高凝及炎症有关。本课题组前期研究发现山莨菪碱对防治化疗性静脉炎有较好疗效，但对导管相关性血栓能否发挥预防作用尚不清楚。本课题将采用酶联免疫吸附法、免疫透射比浊法等技术，检测兔静脉置管模型和临床置管患者使用LMWH、山莨菪碱干预前后血清中血栓形成相关标志物vWF、D-二聚体等、炎性因子hs-CRP等的表达及血液流变学变化，从血管内皮损伤、凝血、血流状态及炎症因子影响等角度对比分析药物干预效果，力求阐明山莨菪碱通过改变血流动力学→减少炎性因子对血管损伤→使低分子肝素发挥抗凝作用、从而影响导管相关性血栓形成的作用机制，为导管相关性血栓形成的防治提供新靶点。本课题对指导静脉导管留置的安全使用具有重要意义。

导管相关性血栓形成是静脉留置导管输液的常见并发症，导致患者住院时间、治疗风险和成本增加。本课题的主要进展和成果如下：.（1）首次报道兔颈外静脉导管留置输液模型的建立，为动物深静脉置管的研究提供相应的方法。.（2）应用留置针致兔耳缘静脉血栓形成动物模型，发现留置针置入后，内皮细胞受到损伤，血栓形成激发纤溶过程；置入1d，vWF、DD浓度升高，光镜下观察已有静脉血栓形成，因此，为预防血栓形成应及早进行干预。随着留置时间的延长，静脉炎症反应及血栓形成逐渐加重，vWF和DD浓度的测定对预测留置针致静脉血栓形成过程有一定的参考价值。.（3）对中心静脉导管置管后怀疑CRBSI患者检测血样本PCT和血清超敏C-反应蛋白hs-CRP的水平，发现血清PCT、hs-CRP水平改变可作为CRBSI的敏感指标，PCT灵敏度、特异度均高于CRP，动态监测PCT水平更有利于为临床早期预防和治疗提供依据。.（4）采用兔颈外静脉导管留置输液模型，观察药物作用下不同留置时间CRT发生情况，发现穿刺时造成的血管内皮细胞损伤和置管后引起的血流改变可能与CRT发生更加密切相关。监测血液FIB浓度变化可为判断CRT发生风险提供依据，FIB水平在留置3天时对判断CRT的敏感度较高，留置5天时对判断CRT的特异度较高。而血小板活性增强可能不是CRT发生的主要原因。.（5）在兔耳缘静脉置入留置针，采用20％甘露醇溶液注射建立血栓形成动物模型。①用低分子量肝素钙皮下注射干预，动态观察vWF、DD值变化，可评估药物预防血栓形成的适宜时机及干预效果；②注射血管部位用2%山莨菪碱霜外涂干预，动态观察TNF-α、D-D、VEGF浓度变化，对血栓形成有提示作用，证实山莨菪碱可降低静脉炎的发生。.（6）采用2%山莨菪碱霜外用预防5-氟尿嘧啶所致化疗性静脉炎，证实能有效减轻静脉炎的发生和局部疼痛，同时可提高患者预防的主动性，有良好的推广价值。