肺动脉栓塞动物模型中血栓形态及血D-二聚体与血栓时相相关性研究

Correlation between the thrombosis form,D-dimer and thrombosis phase in animal models with pulmonary embolism

目的通过制备家兔肺动脉栓塞模型,追踪肺动脉血栓在无外界因素干扰下随时间改变的影像学变化,以及实验室D-二聚体变化曲线,从而为临床诊断急、慢性血栓及治疗方案的选择提供科学依据。方法中国大耳白兔制备肺动脉栓塞模型,于栓塞当天、3 d、7 d、14 d、21 d和28 d分别对家兔进行CTPA扫描和血D-二聚体检测,描述各时段血栓形态变化及分布,同时采集血D-二聚体时间曲线。结果血栓注入早期,血栓形态以Ⅴ型和Ⅰ型血栓居多,其次为Ⅳ型血栓和Ⅱ型;肺动脉栓塞中期:Ⅱ型血栓数量增加,出现Ⅲ型血栓,其余Ⅰ、Ⅳ、Ⅴ型血栓型不同程度减少;栓塞后21~28 d为慢性血栓期,慢性期以Ⅲ型血栓为著,其他各型血栓数量均下降,且明显减小。各型血栓变化:Ⅰ型血栓累及血管面积总和由栓塞当天140.36 mm2下降到栓塞后28 d 13.2 mm2,血栓逐渐减小,部分转变为其他类型;Ⅱ型血栓在栓塞后7~14 d出现一个小的波峰;Ⅲ型血栓急性期未见显示,发生于栓塞中、晚期,随着时间推移,受累血管逐渐增加,最终成为慢性血栓主要类型;Ⅳ型血栓常见于栓塞早期较大血管,后迅速下降,慢性期可由上游血栓脱落而来;Ⅴ型血栓各期均可见,随时间逐渐减少。血D-二聚体峰值出现在家兔栓塞后3~7 d,于14 d左右开始回落,21 d后基本恢复正常。结论各种血栓形态发生于不同的肺栓塞时期,肺动脉栓塞形成是一动态过程,新鲜血栓主要成分为血小板,飘浮于血管腔,较大者或骑跨于血管分叉处,故以Ⅰ型血栓、Ⅳ型血栓为著;Ⅱ型由于血栓脱水减小,附壁于一侧,常见于亚急性期至慢性期;Ⅲ型血栓常见于慢性期,为机化血栓;Ⅴ型血栓各期均可见,故无法单纯根据Ⅴ型形态判断急慢性。D-二聚体峰值基本出现在栓塞后3~7 d,于栓塞后14 d左右开始回落,存在明确曲线,故D-二聚体对肺动脉栓塞的诊断是具有一定价值的,但本组实验采用单因素分析,在临床实践中,患者通常存在多因素影响,均可引起血中D-二聚体升高,故单一依靠血D-二聚体的变化来判断肺动脉血栓的时相并不科学,须结合临床及影像检查,综合分析评价更为可靠。

Objective To investigate the correlation between the thrombosis form,D-dimer and thrombosis phase in animal models with pulmonary embolism,so as to provide scientific basis for the diagnosis and treatment of acute and chronic thrombosis in clinical practice.Methods The animal models with pulmonary embolism were established in Chinese white rabbits.The rabbit models underwent CTPA scans and blood D-dimer level detection on that day,and at 3d,7d,14d,21d and 28d after modelling.The changes and distribution of thrombosis form were observed,and the blood D-dimer time curve was plotted.Results At the early stage of pulmonary embolism,the shape of thrombus was mainly typeⅤand typeⅠ,followed by typeⅣand typeⅡ,and at the middle stage of pulmonary embolism,the number of typeⅡthrombus increased,typeⅢthrombus appeared,and typeⅠ,Ⅳ,Ⅴthrombus was decreased at different degrees.The chronic thrombosis phase was during 21~28 days after embolism,in which,typeⅢthrombus was predominant and the number of other types was decreased significantly.The changes of thrombus types:in typeⅠthrombus,the total area of involving blood vessel was decreased from 140.36mm2 on that day of embolism to 13.2mm2 at 28 days after embolism.The thrombus was gradually decreased and partially changed to other types,and typeⅡthrombus showed a small peak during 7~14 days after embolism,and typeⅢthrombus was not found at acute phase,which occurred in middle and late stages of embolism,the area of affected blood vessels was increased with time,eventually became the main type of chronic thrombosis.The typeⅣthrombus was common in larger blood vessels at early stage and decreased rapidly,which could be detached from the upstream thrombus at chronic phase and could be seen in all phases,then which was gradually decreased with time.The peak of blood D-dimer appeared during 3~7 days after embolism,began to decrease at 14 days after embolism,and decreased to normal levels at 21 days after embolism.Conclusion The pulmonary embolism in rabbits is a dynamic process,and various thrombus types occur at different stages ofpulmonary embolism.The main component of freshthrombus is platelets,floating in the lumen of theblood vessels,and the larger ones riding across thebifurcation of the blood vessels,moreover,typeⅠandⅣare the main types.The peak of D-dimer levelmainly appears during 3~7 days after embolism,which begin to decrease about 14 days after embolism,and D-dimer has certain value in the diagnosis of pulmonary embolism.In clinical practice,patients often have multiple factors including lower extremity venous thrombosis,hypercoagulability state and pulmonary hypertension,which can result in the increase of D-dimer levels,therefor,it is necessary to evaluate the results by combining clinical and imaging examination results.