建立更符合临床的深静脉血栓形成大鼠模型的研究

Establishment of rat model more consistent with clinical deep vein thrombosis

目的通过不同的方法建立深静脉血栓形成大鼠模型,筛选出更稳定、更符合临床的深静脉血栓形成大鼠模型。方法将144只SD大鼠随机分为N、S、V1、V2、V3、V46组,即正常对照组(N组)、假手术组(S组)、不完全阻滞左股静脉血流组(V1组)、不完全阻滞左股静脉血流+左下肢制动组(V2组)、不完全阻滞左股静脉血流+注入10%高渗盐水1 ml组(V3组)、不完全阻滞左股静脉血流+注入凝血酶0.25 U组(V4组),每组24只。于建模后第2、6、10日,分别处死各组大鼠8只,比较各组血栓形成情况,并行病理学分析。结果建模后第2、6、10日,N、S组均未见血栓形成;V1组血栓形成率(0%、12.5%、25%)与N、S组比较差异无统计学意义(P>0.05);V3组血栓形成率(62.5%、87.5%、75%)明显高于N、S、V1、V2(25%、50%、50%)、V4(28.6%、62.5%、37.5%)组(P<0.05);V2、V4组血栓形成率均高于N、S、V1组(P<0.05),而V2、V4两组间的差异无统计学意义(P>0.05)。病理检查可见血栓不同时期的变化及血管再通现象。结论通过不完全阻滞股静脉血流+注入10%高渗盐水的方法,可以建立稳定的、更符合临床的深静脉血栓形成大鼠模型,此模型可用于深静脉血栓形成病理转归及防治的研究。

Objective To establish rat models of deep venous thrombosis by employing different methods,aiming to screen an establishment approach which is more stable and consistent with the clinical prac-tice.Methods One hundred and forty-four Sprague-Dawley rats were randomly and equally divided into 6 groups （N,S,V1 ,V2 ,V3 and V4 ）：The group N defines normal control group.The rats in the group S un-derwent sham operation.In the group V1 ,the left femoral vein of the rats was incompletely ligated.In the group V2 ,the left femoral vein was incompletely ligated with immobilization of the left lower limb.In the group V3 ,the left femoral vein was incompletely ligated in combination with injection of 1 ml of 1 0% hypertonic sa-line from the distal end of the incompletely ligated femoral vein.In the group V4 ,the left femoral vein was in-completely ligated,and then 0.25 U of thrombin was injected slowly from the distal end of the incompletely li-gated femoral vein.On the 2nd,6th and 1 0th day,8 rats from each group were sacrificed,and the femoral vein was collected for observing the formation of the thrombosis and pathological analysis.Results On the day 2,6 and 1 0,no thrombosis was observed in group N or group S.The rate of thrombosis formation in group V1 （0%,1 2.5% and 25% on the day 2,6 and 1 0）did not significantly differ from those in group N and group S （all P 〉0.05）.The rate of thrombosis formation in group V3 （62.5%,87.5% and 75%）was significantly higher than those in groups N,S,V1 ,V2 （25%,50% and 50%）and V4 （28.6%,62.5% and 37.5%） （all P 〈0.05）.The rates of thrombosis formation in groups V2 and V4 were both significantly higher than those in groups N,S and V1 （all P 〈0.05）,but no significant difference was noted between group V2 and group V4 （P 〉0.05）.The changes of thrombosis at different periods and the vascular recanalization were observed bypathological examination.Conclusions A rat model of deep venous thrombosis which is more stable and more consistent with the clinical practice can be established by incomplete ligature of the femoral vein combined with injection of 1 0% hypertonic saline from the distal end of the incompletely ligated femoral vein.This model can be utilized to observe the pathological changes and evaluate the treatment efficacy of deep venous thrombosis.